Small Nucleolar RNAs: Biological Functions and Diseases

Abstract

Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that play a pivotal role in diverse cellular processes and are extensively implicated in the pathophysiology of various diseases. Here, we provide a comprehensive overview of snoRNAs, encompassing their classification, biogenesis, and both canonical and noncanonical functions. Canonical roles include guiding RNA modifications such as 2′-O-methylation, pseudouridylation, and N4-acetylcytidine modification in targeted RNA molecules, as well as facilitating ribosome biogenesis. Noncanonical roles involve regulating mRNA processing, modulating alternative splicing, generating snoRNA-derived small RNAs, and interacting with long noncoding RNAs. Dysregulation of snoRNAs has been implicated in various human diseases, such as cancer, neurodegenerative disorders, cardiovascular diseases, immunity- and inflammation-related conditions, and aging, highlighting their potential as diagnostic and prognostic biomarkers. Advances in high-throughput sequencing, structural biology, and bioinformatics tools have significantly contributed to the detection, screening, and exploration of the intricate biofunctions of snoRNAs. However, despite these technological advancements, challenges remain in unraveling the biological complexity of snoRNAs and translating these findings into clinical applications. This review discusses the current state of snoRNA research, recent technological breakthroughs, and future directions, emphasizing their emerging roles in health and disease.

Keywords

cancer / cardiovascular diseases / nucleic acid-based drugs / neurological diseases / small nucleolar RNAs

References

[1] E. S. Maxwell and M. J. Fournier, “The Small Nucleolar RNAs,” Annual Review of Biochemistry 64 (1995): 897-934.

[2] H. Jorjani, S. Kehr, D. J. Jedlinski, et al., “An Updated human snoRNAome,” Nucleic Acids Research 44, no. 11 (2016): 5068-5082.

[3] G. T. Williams and F. Farzaneh, “Are snoRNAs and snoRNA Host Genes New Players in Cancer?,” Nature Reviews Cancer 12, no. 2 (2012): 84-88.

[4] G. A. Stepanov, J. A. Filippova, A. B. Komissarov, E. V. Kuligina, V. A. Richter, and D. V. Semenov, “Regulatory Role of Small Nucleolar RNAs in human Diseases,” BioMed Research International 2015 (2015): 206849.

[5] D. Tollervey and T. Kiss, “Function and Synthesis of Small Nucleolar RNAs,” Current Opinion in Cell Biology 9, no. 3 (1997): 337-342.

[6] T. Bratkovič, J. Božič, and B. Rogelj, “Functional Diversity of Small Nucleolar RNAs,” Nucleic Acids Research 48, no. 4 (2020): 1627-1651.

[7] H. Xiao, X. Feng, M. Liu, H. Gong, and X. Zhou, “SnoRNA and lncSNHG: Advances of Nucleolar Small RNA Host Gene Transcripts in Anti-tumor Immunity,” Frontiers in Immunology 14 (2023): 1143980.

[8] Y. Shi and J. L. Manley, “The End of the Message: Multiple Protein-RNA Interactions Define the mRNA Polyadenylation Site,” Genes & Development 29, no. 9 (2015): 889-897.

[9] C. Huang, J. Shi, Y. Guo, et al., “A snoRNA Modulates mRNA 3' end Processing and Regulates the Expression of a Subset of mRNAs,” Nucleic Acids Research 45, no. 15 (2017): 8647-8660.

[10] W. Chauhan, S. Sudharshan, S. Kafle, and R. Zennadi, “SnoRNAs: Exploring Their Implication in Human Diseases,” International Journal of Molecular Sciences 25, no. 13 (2024): 7202.

[11] T. Kiss, “Small Nucleolar RNAs: An Abundant Group of Noncoding RNAs With Diverse Cellular Functions,” Cell 109, no. 2 (2002): 145-148.

[12] A.G. Matera, R. M. Terns, and M. P. Terns, “Non-coding RNAs: Lessons From the Small Nuclear and Small Nucleolar RNAs,” Nature Reviews Molecular Cell Biology 8, no. 3 (2007): 209-220.

[13] C. Verheggen, J. Mouaikel, M. Thiry, et al., “Box C/D Small Nucleolar RNA Trafficking Involves Small Nucleolar RNP Proteins, Nucleolar Factors and a Novel Nuclear Domain,” The EMBO Journal 20, no. 19 (2001): 5480.

[14] L. B. Weinstein and J. A. Steitz, “Guided Tours: From Precursor snoRNA to Functional snoRNP,” Current Opinion in Cell Biology 11, no. 3 (1999): 378-384.

[15] S. G. Li, H. Zhou, Y. P. Luo, P. Zhang, and L. H. Qu, “Identification and Functional Analysis of 20 Box H/ACA Small Nucleolar RNAs (snoRNAs) From Schizosaccharomyces Pombe,” Journal of Biological Chemistry 280, no. 16 (2005): 16446-16455.

[16] J. W. Brown, G. P. Clark, D. J. Leader, C. G. Simpson, and T. Lowe, “Multiple snoRNA Gene Clusters From Arabidopsis,” Rna 7, no. 12 (2001): 1817-1832.

[17] D. J. Leader, G. P. Clark, J. Watters, A. F. Beven, P. J. Shaw, and J. W. Brown, “Clusters of Multiple Different Small Nucleolar RNA Genes in Plants Are Expressed as and Processed From Polycistronic Pre-snoRNAs,” Embo Journal 16, no. 18 (1997): 5742-5751.

[18] É. Fafard-Couture, D. Bergeron, S. Couture, S. Abou-Elela, and M. S. Scott, “Annotation of snoRNA Abundance Across human Tissues Reveals Complex snoRNA-host Gene Relationships,” Genome Biology 22, no. 1 (2021): 172.

[19] L. Yang, “Splicing Noncoding RNAs From the inside Out,” Wiley Interdiscip Rev RNA 6, no. 6 (2015): 651-660.

[20] É. Fafard-Couture, D. Bergeron, S. Couture, S. Abou-Elela, and M. S. Scott, “Annotation of snoRNA Abundance Across human Tissues Reveals Complex snoRNA-host Gene Relationships,” Genome Biology 22, no. 1 (2021): 172.

[21] D. Bergeron, L. Faucher-Giguère, A.-K. Emmerichs, et al., “Intronic Small Nucleolar RNAs Regulate Host Gene Splicing Through Base Pairing With Their Adjacent Intronic Sequences,” Genome Biology 24, no. 1 (2023): 160.

[22] G. Chanfreau, P. Legrain, and A. Jacquier, “Yeast RNase III as a Key Processing Enzyme in Small Nucleolar RNAs Metabolism,” Journal of Molecular Biology 284, no. 4 (1998): 975-988.

[23] E. Petfalski, T. Dandekar, Y. Henry, and D. Tollervey, “Processing of the Precursors to Small Nucleolar RNAs and rRNAs Requires Common Components,” Molecular and Cellular Biology 18, no. 3 (1998): 1181-1189.

[24] L. H. Qu, A. Henras, Y. J. Lu, et al., “Seven Novel Methylation Guide Small Nucleolar RNAs Are Processed From a Common Polycistronic Transcript by Rat1p and RNase III in Yeast,” Molecular and Cellular Biology 19, no. 2 (1999): 1144-1158.

[25] G. Dieci, M. Preti, and B. Montanini, “Eukaryotic snoRNAs: A Paradigm for Gene Expression Flexibility,” Genomics 94, no. 2 (2009): 83-88.

[26] É. Fafard-Couture, S. Labialle, and M. S. Scott, “The Regulatory Roles of Small Nucleolar RNAs Within Their Host Locus,” RNA Biology 21, no. 1 (2024): 1-11.

[27] T. Bratkovič and B. Rogelj, “Biology and Applications of Small Nucleolar RNAs,” Cellular and Molecular Life Sciences 68, no. 23 (2011): 3843-3851.

[28] W. Filipowicz and V. Pogacić, “Biogenesis of Small Nucleolar Ribonucleoproteins,” Current Opinion in Cell Biology 14, no. 3 (2002): 319-327.

[29] J. P. Bachellerie, J. Cavaillé, and A. Hüttenhofer, “The Expanding snoRNA World,” Biochimie 84, no. 8 (2002): 775-790.

[30] K. T. Tycowski, M. D. Shu, A. Kukoyi, and J. A. Steitz, “A Conserved WD40 Protein Binds the Cajal Body Localization Signal of scaRNP Particles,” Molecular Cell 34, no. 1 (2009): 47-57.

[31] P. Richard, X. Darzacq, E. Bertrand, B. E. Jády, C. Verheggen, and T. Kiss, “A Common Sequence Motif Determines the Cajal Body-specific Localization of Box H/ACA scaRNAs,” Embo Journal 22, no. 16 (2003): 4283-4293.

[32] A. Marnef, P. Richard, N. Pinzón, and T. Kiss, “Targeting Vertebrate Intron-encoded Box C/D 2'-O-methylation Guide RNAs Into the Cajal Body,” Nucleic Acids Research 42, no. 10 (2014): 6616-6629.

[33] S. Ojha, S. Malla, and S. M. Lyons, “snoRNPs: Functions in Ribosome Biogenesis,” Biomolecules 10, no. 5 (2020): 783.

[34] S. F. Webster and H. Ghalei, “Maturation of Small Nucleolar RNAs: From Production to Function,” RNA Biology 20, no. 1 (2023): 715-736.

[35] S. Deng, P. Yi, M. Xu, Q. Yi, and J. Feng, “Dysfunctional Gene Splicing in Glucose Metabolism May Contribute to Alzheimer's Disease,” Chinese Medical Journal 136, no. 6 (2023): 666-675.

[36] Y. Tao, Q. Zhang, H. Wang, X. Yang, and H. Mu, “Alternative Splicing and Related RNA Binding Proteins in human Health and Disease,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 26.

[37] K. Gawade, P. Plewka, S. J. Häfner, et al., “FUS Regulates a Subset of snoRNA Expression and Modulates the Level of rRNA Modifications,” Scientific Reports 13, no. 1 (2023): 2974.

[38] G. W. Jawdekar and R. W. Henry, “Transcriptional Regulation of human Small Nuclear RNA Genes,” Biochimica Et Biophysica Acta 1779, no. 5 (2008): 295-305.

[39] S. Nabavi and R. N. Nazar, “U3 snoRNA Promoter Reflects the RNA's Function in Ribosome Biogenesis,” Current Genetics 54, no. 4 (2008): 175-184.

[40] G. Dieci, G. Fiorino, M. Castelnuovo, M. Teichmann, and A. Pagano, “The Expanding RNA Polymerase III Transcriptome,” Trends in Genetics 23, no. 12 (2007): 614-622.

[41] T. Li, X. Zhou, X. Wang, D. Zhu, and Y. Zhang, “Identification and Characterization of human snoRNA Core Promoters,” Genomics 96, no. 1 (2010): 50-56.

[42] B. Zhang, D. Han, Y. Korostelev, et al., “Changes in snoRNA and snRNA Abundance in the Human, Chimpanzee, Macaque, and Mouse Brain,” Genome Biology and Evolution 8, no. 3 (2016): 840-850.

[43] X. Y. Dong, P. Guo, J. Boyd, et al., “Implication of snoRNA U50 in human Breast Cancer,” Journal of Genetics and Genomics 36, no. 8 (2009): 447-454.

[44] M. Penzo, R. Clima, D. Trerè, and L. Montanaro, “Separated Siamese Twins: Intronic Small Nucleolar RNAs and Matched Host Genes May be Altered in Conjunction or Separately in Multiple Cancer Types,” Cells 9, no. 2 (2020): 387.

[45] Y. P. Mei, J. P. Liao, J. Shen, et al., “Small Nucleolar RNA 42 Acts as an Oncogene in Lung Tumorigenesis,” Oncogene 31, no. 22 (2012): 2794-2804.

[46] T. Hirose, M. D. Shu, and J. A. Steitz, “Splicing-dependent and -independent Modes of Assembly for Intron-encoded Box C/D snoRNPs in Mammalian Cells,” Molecular Cell 12, no. 1 (2003): 113-123.

[47] N. J. Watkins and M. T. Bohnsack, “The Box C/D and H/ACA snoRNPs: Key Players in the Modification, Processing and the Dynamic Folding of Ribosomal RNA,” Wiley Interdiscip Rev RNA 3, no. 3 (2012): 397-414.

[48] F. Spenkuch, Y. Motorin, and M. Helm, “Pseudouridine: Still Mysterious, but Never a Fake (uridine)!,” RNA Biology 11, no. 12 (2014): 1540-1554.

[49] M. Charette and M. W. Gray, “Pseudouridine in RNA: What, Where, How, and Why,” Iubmb Life 49, no. 5 (2000): 341-351.

[50] X. Darzacq and T. Kiss, “Processing of Intron-encoded Box C/D Small Nucleolar RNAs Lacking a 5',3'-terminal Stem Structure,” Molecular and Cellular Biology 20, no. 13 (2000): 4522-4531.

[51] T. Kiss, “Small Nucleolar RNA-guided Post-transcriptional Modification of Cellular RNAs,” Embo Journal 20, no. 14 (2001): 3617-3622.

[52] K. S. McKeegan, C. M. Debieux, S. Boulon, E. Bertrand, and N. J. Watkins, “A Dynamic Scaffold of Pre-snoRNP Factors Facilitates human Box C/D snoRNP Assembly,” Molecular and Cellular Biology 27, no. 19 (2007): 6782-6793.

[53] Z. Kiss-László, Y. Henry, J.-P. Bachellerie, M. Caizergues-Ferrer, and T. Kiss, “Site-Specific Ribose Methylation of Preribosomal RNA: A Novel Function for Small Nucleolar RNAs,” Cell 85, no. 7 (1996): 1077-1088.

[54] G. Yu, Y. Zhao, and H. Li, “The Multistructural Forms of Box C/D ribonucleoprotein Particles,” Rna 24, no. 12 (2018): 1625-1633.

[55] B. A. Elliott, H. T. Ho, S. V. Ranganathan, et al., “Modification of Messenger RNA by 2'-O-methylation Regulates Gene Expression in Vivo,” Nature Communications 10, no. 1 (2019): 3401.

[56] P. P. Dennis and A. Omer, “Small Non-coding RNAs in Archaea,” Current Opinion in Microbiology 8, no. 6 (2005): 685-694.

[57] P. Vitali and T. Kiss, “Cooperative 2'-O-methylation of the Wobble Cytidine of human Elongator tRNA(Met)(CAT) by a Nucleolar and a Cajal Body-specific Box C/D RNP,” Genes & development 33, no. 13-14 (2019): 741-746.

[58] B. Lu, X. Chen, X. Liu, et al., “C/D Box Small Nucleolar RNA SNORD104 Promotes Endometrial Cancer by Regulating the 2'-O-methylation of PARP1,” Journal of Translational Medicine 20, no. 1 (2022): 618.

[59] A. M. Kiss, B. E. Jády, E. Bertrand, and T. Kiss, “Human Box H/ACA Pseudouridylation Guide RNA Machinery,” Molecular and Cellular Biology 24, no. 13 (2004): 5797-5807.

[60] C. Wang, C. C. Query, and U. T. Meier, “Immunopurified Small Nucleolar ribonucleoprotein Particles Pseudouridylate rRNA Independently of Their Association With Phosphorylated Nopp140,” Molecular and Cellular Biology 22, no. 24 (2002): 8457-8466.

[61] C. Bousquet-Antonelli, Y. Henry, J. P. G'Elugne, M. Caizergues-Ferrer, and T. Kiss, “A Small Nucleolar RNP Protein Is Required for Pseudouridylation of Eukaryotic Ribosomal RNAs,” Embo Journal 16, no. 15 (1997): 4770-4776.

[62] H. Jin, J. P. Loria, and P. B. Moore, “Solution Structure of an rRNA Substrate Bound to the Pseudouridylation Pocket of a Box H/ACA snoRNA,” Molecular Cell 26, no. 2 (2007): 205-215.

[63] J. Karijolich, A. Kantartzis, and Y. T. Yu, “RNA Modifications: A Mechanism That Modulates Gene Expression,” Methods in Molecular Biology 629 (2010): 1-19.

[64] A. K. Henras, C. Plisson-Chastang, O. Humbert, Y. Romeo, and Y. Henry, “Synthesis, Function, and Heterogeneity of snoRNA-Guided Posttranscriptional Nucleoside Modifications in Eukaryotic Ribosomal RNAs,” Enzymes 41 (2017): 169-213.

[65] M. L. Bortolin-Cavaillé, A. Quillien, S. Thalalla Gamage, et al., “Probing Small Ribosomal Subunit RNA Helix 45 Acetylation Across Eukaryotic Evolution,” Nucleic Acids Research 50, no. 11 (2022): 6284-6299.

[66] Q. Wang, Y. Yuan, Q. Zhou, et al., “RNA N4-acetylcytidine Modification and Its Role in Health and Diseases,” MedComm 6, no. 1 (2025): e70015.

[67] H. F. Noller, V. Hoffarth, and L. Zimniak, “Unusual Resistance of Peptidyl Transferase to Protein Extraction Procedures,” Science 256, no. 5062 (1992): 1416-1419.

[68] M. M. Yusupov, G. Z. Yusupova, A. Baucom, et al., “Crystal Structure of the Ribosome at 5.5 Å Resolution,” Science 292, no. 5518 (2001): 883-896.

[69] H. H. Weetall. Preparation of Immobilized Proteins Covalently Coupled through Silane Coupling Agents to Inorganic Supports. In: Bittar EE, Danielsson B, Bülow L, eds. “Advances in Molecular and Cell Biology”. (Elsevier, 1996): 161-192.

[70] S. Klinge and J. L. Woolford, “Ribosome Assembly Coming Into Focus,” Nature Reviews Molecular Cell Biology 20, no. 2 (2019): 116-131.

[71] Z. Shajani, M. T. Sykes, and J. R. Williamson, “Assembly of Bacterial Ribosomes,” Annual Review of Biochemistry 80 (2011): 501-526.

[72] L. M. Dutca, J. E. Gallagher, and S. J. Baserga, “The Initial U3 snoRNA:Pre-rRNA Base Pairing Interaction Required for Pre-18S rRNA Folding Revealed by in Vivo Chemical Probing,” Nucleic Acids Research 39, no. 12 (2011): 5164-5180.

[73] C. Helmer, R. Eibach, P. C. Tegtmeyer, E. Humann-Ziehank, and M. Ganter, “Survey of Schmallenberg Virus (SBV) Infection in German Goat Flocks,” Epidemiology and Infection 141, no. 11 (2013): 2335-2345.

[74] H. R. Vos, R. Bax, A. W. Faber, J. C. Vos, and H. A. Raué, “U3 snoRNP and Rrp5p Associate Independently With Saccharomyces Cerevisiae 35S Pre-rRNA, but Rrp5p Is Essential for Association of Rok1p,” Nucleic Acids Research 32, no. 19 (2004): 5827-5833.

[75] A. J. Turner, A. A. Knox, J. L. Prieto, B. McStay, and N. J. Watkins, “A Novel Small-subunit Processome Assembly Intermediate That Contains the U3 snoRNP, Nucleolin, RRP5, and DBP4,” Molecular and Cellular Biology 29, no. 11 (2009): 3007-3017.

[76] J. Song, L. Dong, H. Sun, et al., “CRISPR-free, Programmable RNA Pseudouridylation to Suppress Premature Termination Codons,” Molecular Cell 83, no. 1 (2023): 139-155.

[77] E. Sharma, T. Sterne-Weiler, D. O'Hanlon, and B. J. Blencowe, “Global Mapping of Human RNA-RNA Interactions,” Molecular Cell 62, no. 4 (2016): 618-626.

[78] M. Helm and Y. Motorin, “Detecting RNA Modifications in the Epitranscriptome: Predict and Validate,” Nature Reviews Genetics 18, no. 5 (2017): 275-291.

[79] S. Schwartz, “Cracking the Epitranscriptome,” Rna 22, no. 2 (2016): 169-174.

[80] B. S. Zhao, I. A. Roundtree, and C. He, “Post-transcriptional Gene Regulation by mRNA Modifications,” Nature Reviews Molecular Cell Biology 18, no. 1 (2017): 31-42.

[81] B. Linder and S. R. Jaffrey, “Discovering and Mapping the Modified Nucleotides That Comprise the Epitranscriptome of mRNA,” Cold Spring Harbor Perspectives in Biology 11, no. 6 (2019): a032201.

[82] A. Sas-Chen, J. M. Thomas, D. Matzov, et al., “Dynamic RNA Acetylation Revealed by Quantitative Cross-evolutionary Mapping,” Nature 583, no. 7817 (2020): 638-643.

[83] R. Nir, T. P. Hoernes, H. Muramatsu, et al., “A Systematic Dissection of Determinants and Consequences of snoRNA-guided Pseudouridylation of human mRNA,” Nucleic Acids Research 50, no. 9 (2022): 4900-4916.

[84] G. E. Ghanim, Z. Sekne, S. Balch, A. M. van Roon, and T. H. D. Nguyen, “2.7 Å Cryo-EM Structure of human Telomerase H/ACA ribonucleoprotein,” Nature Communications 15, no. 1 (2024): 746.

[85] J. Feng, J. Zhou, Y. Lin, and W. Huang, “hnRNP A1 in RNA Metabolism Regulation and as a Potential Therapeutic Target,” Frontiers in Pharmacology 13 (2022): 986409.

[86] I. Ullah, W. Sun, L. Tang, and J. Feng, “Roles of Smads Family and Alternative Splicing Variants of Smad4 in Different Cancers,” Journal of Cancer 9, no. 21 (2018): 4018-4028.

[87] J. Zhang, X. Xu, H. Deng, L. Liu, Y. Xiang, and J. Feng, “Overcoming Cancer Drug-resistance Calls for Novel Strategies Targeting Abnormal Alternative Splicing,” Pharmacology & Therapeutics 261 (2024): 108697.

[88] S. Kishore and S. Stamm, “Regulation of Alternative Splicing by snoRNAs,” Cold Spring Harbor Symposia on Quantitative Biology 71 (2006): 329-334.

[89] S. Kishore and S. Stamm, “The snoRNA HBII-52 Regulates Alternative Splicing of the Serotonin Receptor 2C,” Science 311, no. 5758 (2006): 230-232.

[90] S. Kishore, A. Khanna, Z. Zhang, et al., “The snoRNA MBII-52 (SNORD 115) Is Processed Into Smaller RNAs and Regulates Alternative Splicing,” Human Molecular Genetics 19, no. 7 (2010): 1153-1164.

[91] S. Lykke-Andersen, B. K. Ardal, A. K. Hollensen, C. K. Damgaard, and T. H. Jensen, “Box C/D snoRNP Autoregulation by a Cis-Acting snoRNA in the NOP56 Pre-mRNA,” Molecular Cell 72, no. 1 (2018): 99-111.

[92] B. Bao, M. Tian, X. Wang, et al., “SNORA37/CMTR1/ELAVL1 feedback Loop Drives Gastric Cancer Progression via Facilitating CD44 Alternative Splicing,” Journal of Experimental & Clinical Cancer Research 44, no. 1 (2025): 15.

[93] M. Falaleeva and S. Stamm, “Processing of snoRNAs as a New Source of Regulatory Non-coding RNAs: SnoRNA Fragments Form a New Class of Functional RNAs,” BioEssays 35, no. 1 (2013): 46-54.

[94] R. J. Taft, E. A. Glazov, T. Lassmann, Y. Hayashizaki, P. Carninci, and J. S. Mattick, “Small RNAs Derived From snoRNAs,” Rna 15, no. 7 (2009): 1233-1240.

[95] C. Ender, A. Krek, M. R. Friedländer, et al., “A human snoRNA With microRNA-Like Functions,” Molecular Cell 32, no. 4 (2008): 519-528.

[96] M. Brameier, A. Herwig, R. Reinhardt, L. Walter, and J. Gruber, “Human Box C/D snoRNAs With miRNA Like Functions: Expanding the Range of Regulatory RNAs,” Nucleic Acids Research 39, no. 2 (2011): 675-686.

[97] R. K. Gudipati, Z. Xu, A. Lebreton, et al., “Extensive Degradation of RNA Precursors by the Exosome in Wild-type Cells,” Molecular Cell 48, no. 3 (2012): 409-421.

[98] C. Han, L. Y. Sun, X. Q. Luo, et al., “Chromatin-associated Orphan snoRNA Regulates DNA Damage-mediated Differentiation via a Non-canonical Complex,” Cell Reports 38, no. 13 (2022): 110421.

[99] Y. Abel and M. Rederstorff, “SnoRNAs and the Emerging Class of sdRNAs: Multifaceted Players in Oncogenesis,” Biochimie 164 (2019): 17-21.

[100] A. B. Coley, A. N. Stahly, M. V. Kasukurthi, et al., “MicroRNA-Like snoRNA-Derived RNAs (sdRNAs) Promote Castration-Resistant Prostate Cancer,” Cells 11, no. 8 (2022): 1302.

[101] Z. Deng, C. Li, S. Hu, et al., “sdRNA-D43 Derived From Small Nucleolar RNA snoRD43 Improves Chondrocyte Senescence and Osteoarthritis Progression by Negatively Regulating PINK1/Parkin-mediated Mitophagy Pathway via Dual-targeting NRF1 and WIPI2,” Cell Communication and Signaling 23, no. 1 (2025): 77.

[102] C. L. Holley and V. K. Topkara, “An Introduction to Small Non-coding RNAs: MiRNA and snoRNA,” Cardiovascular Drugs and Therapy 25, no. 2 (2011): 151-159.

[103] M. Falaleeva, A. Pages, Z. Matuszek, et al., “Dual Function of C/D Box Small Nucleolar RNAs in rRNA Modification and Alternative Pre-mRNA Splicing,” PNAS 113, no. 12 (2016): E1625-1634.

[104] T. Bratkovič, M. Modic, G. Camargo Ortega, M. Drukker, and B. Rogelj, “Neuronal Differentiation Induces SNORD115 Expression and Is Accompanied by Post-transcriptional Changes of Serotonin Receptor 2c mRNA,” Scientific Reports 8, no. 1 (2018): 5101.

[105] C. M. Burns, H. Chu, S. M. Rueter, et al., “Regulation of Serotonin-2C Receptor G-protein Coupling by RNA Editing,” Nature 387, no. 6630 (1997): 303-308.

[106] M. S. Scott, M. Ono, K. Yamada, A. Endo, G. J. Barton, and A. I. Lamond, “Human Box C/D snoRNA Processing Conservation Across Multiple Cell Types,” Nucleic Acids Research 40, no. 8 (2012): 3676-3688.

[107] Y. H. Xing, R. W. Yao, Y. Zhang, et al., “SLERT Regulates DDX21 Rings Associated With Pol I Transcription,” Cell 169, no. 4 (2017): 664-678.

[108] H. Wu, Q.-F. Yin, Z. Luo, et al., “Unusual Processing Generates <Em>SPA</Em>LncRNAs That Sequester Multiple RNA Binding Proteins,” Molecular Cell 64, no. 3 (2016): 534-548.

[109] C. M. Smith and J. A. Steitz, “Classification of gas5 as a Multi-small-nucleolar-RNA (snoRNA) Host Gene and a Member of the 5'-terminal Oligopyrimidine Gene family Reveals Common Features of snoRNA Host Genes,” Molecular and Cellular Biology 18, no. 12 (1998): 6897-6909.

[110] M. Louca and V. Gkretsi, “LincRNAs and snoRNAs in Breast Cancer Cell Metastasis: The Unknown Players,” Cancers (Basel) 14, no. 18 (2022): 4528.

[111] Q. F. Yin, L. Yang, Y. Zhang, et al., “Long Noncoding RNAs With snoRNA Ends,” Molecular Cell 48, no. 2 (2012): 219-230.

[112] X. Su, C. Feng, S. Wang, et al., “The Noncoding RNAs SNORD50A and SNORD50B-mediated TRIM21-GMPS Interaction Promotes the Growth of p53 Wild-type Breast Cancers by Degrading p53,” Cell Death and Differentiation 28, no. 8 (2021): 2450-2464.

[113] K. Yoshida, S. Toden, W. Weng, et al., “SNORA21 - An Oncogenic Small Nucleolar RNA, With a Prognostic Biomarker Potential in Human Colorectal Cancer,” EBioMedicine 22 (2017): 68-77.

[114] Y. Zhuo, S. Li, W. Hu, et al., “Targeting SNORA38B Attenuates Tumorigenesis and Sensitizes Immune Checkpoint Blockade in Non-small Cell Lung Cancer by Remodeling the Tumor Microenvironment via Regulation of GAB2/AKT/mTOR Signaling Pathway,” Journal for ImmunoTherapy of Cancer 10, no. 5 (2022): e004113.

[115] World Health Organization. Global Cancer Observatory. World Health Organization. Updated 2022. Accessed May 5, 2024, https://gco.iarc.who.int/en.

[116] J. Liang, G. Li, J. Liao, et al., “Non-coding Small Nucleolar RNA SNORD17 Promotes the Progression of Hepatocellular Carcinoma Through a Positive Feedback Loop Upon p53 Inactivation,” Cell Death and Differentiation 29, no. 5 (2022): 988-1003.

[117] C. Li, L. Wu, P. Liu, et al., “The C/D Box Small Nucleolar RNA SNORD52 Regulated by Upf1 Facilitates Hepatocarcinogenesis by Stabilizing CDK1,” Theranostics 10, no. 20 (2020): 9348-9363.

[118] L. Wu, J. Zheng, P. Chen, Q. Liu, and Y. Yuan, “Small Nucleolar RNA ACA11 Promotes Proliferation, Migration and Invasion in Hepatocellular Carcinoma by Targeting the PI3K/AKT Signaling Pathway,” Biomedicine & Pharmacotherapy 90 (2017): 705-712.

[119] H. Wang, P. Ma, P. Liu, B. Chen, and Z. Liu, “Small Nucleolar RNA U2_19 Promotes Hepatocellular Carcinoma Progression by Regulating Wnt/β-catenin Signaling,” Biochemical and Biophysical Research Communications 500, no. 2 (2018): 351-356.

[120] L. Cui, K. Nakano, S. Obchoei, et al., “Small Nucleolar Noncoding RNA SNORA23, Up-Regulated in Human Pancreatic Ductal Adenocarcinoma, Regulates Expression of Spectrin Repeat-Containing Nuclear Envelope 2 to Promote Growth and Metastasis of Xenograft Tumors in Mice,” Gastroenterology 153, no. 1 (2017): 292-306.

[121] Q. Xie, D. Zhang, H. Ye, Z. Wu, Y. Sun, and H. Shen, “Identification of Key snoRNAs Serves as Biomarkers for Hepatocellular Carcinoma by Bioinformatics Methods,” Medicine 101, no. 39 (2022): e30813.

[122] Y. Gu, Z. Yi, Z. Zhou, et al., “SNORD88B-mediated WRN Nucleolar Trafficking Drives Self-renewal in Liver Cancer Initiating Cells and Hepatocarcinogenesis,” Nature Communications 15, no. 1 (2024): 6730.

[123] X. Zhao, G. Chen, Y. Wu, et al., “TEP SNORD12B, SNORA63, and SNORD14E as Novel Biomarkers for hepatitis B Virus-related Hepatocellular Carcinoma (HBV-related HCC),” Cancer Cell International 24, no. 1 (2024): 3.

[124] F. Abu Rous, E. K. Singhi, A. Sridhar, M. S. Faisal, and A. Desai, “Lung Cancer Treatment Advances in 2022,” Cancer Investigation 41, no. 1 (2023): 12-24.

[125] N. E. Mourksi, C. Morin, T. Fenouil, J. J. Diaz, and V. Marcel, “snoRNAs Offer Novel Insight and Promising Perspectives for Lung Cancer Understanding and Management,” Cells 9, no. 3 (2020): 541.

[126] G. Tang, Z. Zeng, W. Sun, et al., “Small Nucleolar RNA 71A Promotes Lung Cancer Cell Proliferation, Migration and Invasion via MAPK/ERK Pathway,” Journal of Cancer 10, no. 10 (2019): 2261-2275.

[127] H. Yu, L. Tian, L. Yang, S. Liu, S. Wang, and J. Gong, “Knockdown of SNORA47 Inhibits the Tumorigenesis of NSCLC via Mediation of PI3K/Akt Signaling Pathway,” Frontiers in Oncology 11 (2021): 620213.

[128] J. Liao, L. Yu, Y. Mei, et al., “Small Nucleolar RNA Signatures as Biomarkers for Non-small-cell Lung Cancer,” Molecular Cancer 9 (2010): 198.

[129] A. N. Giaquinto, H. Sung, K. D. Miller, et al., “Breast Cancer Statistics, 2022,” CA: A Cancer Journal for Clinicians 72, no. 6 (2022): 524-541.

[130] H. Su, T. Xu, S. Ganapathy, et al., “Elevated snoRNA Biogenesis Is Essential in Breast Cancer,” Oncogene 33, no. 11 (2014): 1348-1358.

[131] X. Y. Dong, C. Rodriguez, P. Guo, et al., “SnoRNA U50 Is a Candidate Tumor-suppressor Gene at 6q14.3 With a Mutation Associated With Clinically Significant Prostate Cancer,” Human Molecular Genetics 17, no. 7 (2008): 1031-1042.

[132] Y. Sun, E. Chen, Y. Li, et al., “H/ACA Box Small Nucleolar RNA 7B Acts as an Oncogene and a Potential Prognostic Biomarker in Breast Cancer,” Cancer Cell International 19 (2019): 125.

[133] S. Li, Z. Jin, X. Song, et al., “The Small Nucleolar RNA SNORA51 Enhances Breast Cancer Stem Cell-Like Properties via the RPL3/NPM1/c-MYC Pathway,” Molecular Carcinogenesis 63, no. 6 (2024): 1117-1132.

[134] X. Li, X. Zhao, L. Xie, X. Song, and X. Song, “Identification of Four snoRNAs (SNORD16, SNORA73B, SCARNA4, and SNORD49B) as Novel Non-invasive Biomarkers for Diagnosis of Breast Cancer,” Cancer Cell International 24, no. 1 (2024): 55.

[135] D. Escuin, O. Bell, B. García-Valdecasas, et al., “Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients,” International Journal of Molecular Sciences 25, no. 7 (2024): 3982.

[136] J. N. Li, Z. J. Loh, H. W. Chen, I. Y. Lee, J. H. Tsai, and P. S. Chen, “SnoRNA U50A Mediates Everolimus Resistance in Breast Cancer Through mTOR Downregulation,” Translational Oncology 48 (2024): 102062.

[137] A. Pacilli, C. Ceccarelli, D. Treré, and L. Montanaro, “SnoRNA U50 Levels Are Regulated by Cell Proliferation and rRNA Transcription,” International Journal of Molecular Sciences 14, no. 7 (2013): 14923-14935.

[138] Y. Liu, C. Zhao, G. Wang, et al., “SNORD1C maintains Stemness and 5-FU Resistance by Activation of Wnt Signaling Pathway in Colorectal Cancer,” Cell Death Discovery 8, no. 1 (2022): 200.

[139] L. Shen, C. Lin, W. Lu, et al., “Involvement of the Oncogenic Small Nucleolar RNA SNORA24 in Regulation of p53 Stability in Colorectal Cancer,” Cell Biology and Toxicology 39, no. 4 (2023): 1377-1394.

[140] D. Zhang, J. Zhou, J. Gao, et al., “Targeting snoRNAs as an Emerging Method of Therapeutic Development for Cancer,” American Journal of Cancer Research 9, no. 8 (2019): 1504-1516.

[141] X. Liu, H. Zhang, Y. Fan, et al., “SNORA28 Promotes Proliferation and Radioresistance in Colorectal Cancer Cells Through the STAT3 Pathway by Increasing H3K9 Acetylation in the LIFR Promoter,” Advanced Science (Weinh) 11, no. 32 (2024): e2405332.

[142] J. Gómez-Matas, S. Duran-Sanchon, J. J. Lozano, et al., “SnoRNA Profiling in Colorectal Cancer and Assessment of Non-invasive Biomarker Capacity by ddPCR in Fecal Samples,” Iscience 27, no. 3 (2024): 109283.

[143] L. S. Chang, S. Y. Lin, A. S. Lieu, and T. L. Wu, “Differential Expression of human 5S snoRNA Genes,” Biochemical and Biophysical Research Communications 299, no. 2 (2002): 196-200.

[144] C. Xu, G. Chen, B. Yu, et al., “TRIM24 Cooperates With Ras Mutation to Drive Glioma Progression Through snoRNA Recruitment of PHAX and DNA-PKcs,” Advanced Science (Weinh) 11, no. 29 (2024): e2400023.

[145] Y. Li, S. Yu, X. Wang, et al., “SRPK1 facilitates Tumor Cell Growth via Modulating the Small Nucleolar RNA Expression in Gastric Cancer,” Journal of Cellular Physiology 234, no. 8 (2019): 13582-13591.

[146] F. Zhou, Y. Liu, C. Rohde, et al., “AML1-ETO Requires Enhanced C/D Box snoRNA/RNP Formation to Induce Self-renewal and Leukaemia,” Nature Cell Biology 19, no. 7 (2017): 844-855.

[147] K. J. Teittinen, A. Laiho, A. Uusimäki, J. P. Pursiheimo, A. Gyenesei, and O. Lohi, “Expression of Small Nucleolar RNAs in Leukemic Cells,” Cellular Oncology (Dordrecht) 36, no. 1 (2013): 55-63.

[148] H. Yun, J. Zoller, F. Zhou, et al., “The Landscape of RNA-chromatin Interaction Reveals Small Non-coding RNAs as Essential Mediators of Leukemia Maintenance,” Leukemia 38, no. 8 (2024): 1688-1698.

[149] W. Valleron, E. Laprevotte, E. F. Gautier, et al., “Specific Small Nucleolar RNA Expression Profiles in Acute Leukemia,” Leukemia 26, no. 9 (2012): 2052-2060.

[150] T. Liuksiala, K. J. Teittinen, K. Granberg, et al., “Overexpression of SNORD114-3 Marks Acute Promyelocytic Leukemia,” Leukemia 28, no. 1 (2014): 233-236.

[151] H. Wang, W. Qian, Y. Han, and P. Qian, “Small Noncoding RNAs Play Superior Roles in Maintaining Hematopoietic Stem Cell Homeostasis,” Blood Science 4, no. 3 (2022): 125-132.

[152] C. Pauli, Y. Liu, C. Rohde, et al., “Site-specific Methylation of 18S Ribosomal RNA by SNORD42A Is Required for Acute Myeloid Leukemia Cell Proliferation,” Blood 135, no. 23 (2020): 2059-2070.

[153] C. Saygin and H. E. Carraway, “Current and Emerging Strategies for Management of Myelodysplastic Syndromes,” Blood Reviews 48 (2021): 100791.

[154] M. Sébert, M. Passet, A. Raimbault, et al., “Germline DDX41 Mutations Define a Significant Entity Within Adult MDS/AML Patients,” Blood 134, no. 17 (2019): 1441-1444.

[155] T. M. Chlon, E. Stepanchick, C. E. Hershberger, et al., “Germline DDX41 Mutations Cause Ineffective Hematopoiesis and Myelodysplasia,” Cell Stem Cell 28, no. 11 (2021): 1966-1981.

[156] T. Tsukamoto, M. D. Gearhart, S. Kim, G. Mekonnen, C. A. Spike, and D. Greenstein, “Insights Into the Involvement of Spliceosomal Mutations in Myelodysplastic Disorders From Analysis of SACY-1/DDX41 in Caenorhabditis elegans,” Genetics 214, no. 4 (2020): 869-893.

[157] M. Lewinsohn, A. L. Brown, L. M. Weinel, et al., “Novel Germ Line DDX41 Mutations Define Families With a Lower Age of MDS/AML Onset and Lymphoid Malignancies,” Blood 127, no. 8 (2016): 1017-1023.

[158] J. J. C. Cheah, C. N. Hahn, D. K. Hiwase, H. S. Scott, and A. L. Brown, “Myeloid Neoplasms With Germline DDX41 Mutation,” International Journal of Hematology 106, no. 2 (2017): 163-174.

[159] M. T. Heemels, “Neurodegenerative Diseases,” Nature 539, no. 7628 (2016): 179.

[160] K. S. Sheinerman and S. R. Umansky, “Early Detection of Neurodegenerative Diseases: Circulating Brain-enriched microRNA,” Cell Cycle 12, no. 1 (2013): 1-2.

[161] C. R. Jack, M. S. Albert, D. S. Knopman, et al., “Introduction to the Recommendations From the National Institute on Aging-Alzheimer's Association Workgroups on Diagnostic Guidelines for Alzheimer's Disease,” Alzheimers Dement 7, no. 3 (2011): 257-262.

[162] G. M. McKhann, D. S. Knopman, H. Chertkow, et al., “The Diagnosis of Dementia due to Alzheimer's Disease: Recommendations From the National Institute on Aging-Alzheimer's Association Workgroups on Diagnostic Guidelines for Alzheimer's Disease,” Alzheimers Dement 7, no. 3 (2011): 263-269.

[163] R. Ciurleo, G. Di Lorenzo, P. Bramanti, and S. Marino, “Magnetic Resonance Spectroscopy: An in Vivo Molecular Imaging Biomarker for Parkinson's Disease?,” BioMed research international 2014 (2014): 519816.

[164] G. A. Calin and C. M. Croce, “MicroRNA Signatures in human Cancers,” Nature Reviews Cancer 6, no. 11 (2006): 857-866.

[165] M. Grasso, P. Piscopo, A. Confaloni, and M. A. Denti, “Circulating miRNAs as Biomarkers for Neurodegenerative Disorders,” Molecules (Basel, Switzerland) 19, no. 5 (2014): 6891-6910.

[166] V. Di Pietro, M. Ragusa, D. Davies, et al., “MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury,” Journal of Neurotrauma 34, no. 11 (2017): 1948-1956.

[167] W. A. Decatur and M. J. Fournier, “rRNA Modifications and Ribosome Function,” Trends in Biochemical Sciences 27, no. 7 (2002): 344-351.

[168] Y. J. Crow, H. Marshall, G. I. Rice, et al., “Leukoencephalopathy With Calcifications and Cysts: Genetic and Phenotypic Spectrum,” American Journal of Medical Genetics. Part A 185, no. 1 (2021): 15-25.

[169] P. Labrune, C. Lacroix, F. Goutières, et al., “Extensive Brain Calcifications, Leukodystrophy, and Formation of Parenchymal Cysts: A New Progressive Disorder due to Diffuse Cerebral Microangiopathy,” Neurology 46, no. 5 (1996): 1297-1301.

[170] R. Gstir, S. Schafferer, M. Scheideler, et al., “Generation of a Neuro-specific Microarray Reveals Novel Differentially Expressed Noncoding RNAs in Mouse Models for Neurodegenerative Diseases,” Rna 20, no. 12 (2014): 1929-1943.

[171] B. I. Laufer, K. Mantha, M. L. Kleiber, E. J. Diehl, S. M. Addison, and S. M. Singh, “Long-lasting Alterations to DNA Methylation and ncRNAs Could Underlie the Effects of Fetal Alcohol Exposure in Mice,” Disease Models & Mechanisms 6, no. 4 (2013): 977-992.

[172] E. M. Jenkinson, M. P. Rodero, P. R. Kasher, et al., “Mutations in SNORD118 Cause the Cerebral Microangiopathy Leukoencephalopathy With Calcifications and Cysts,” Nature Genetics 48, no. 10 (2016): 1185-1192.

[173] F. Jenck, M. Bös, J. Wichmann, H. Stadler, J. R. Martin, and J. L. Moreau, “The Role of 5-HT2C Receptors in Affective Disorders,” Expert Opinion on Investigational Drugs 7, no. 10 (1998): 1587-1599.

[174] Y. G. Ni and R. Miledi, “Blockage of 5HT2C Serotonin Receptors by Fluoxetine (Prozac),” PNAS 94, no. 5 (1997): 2036-2040.

[175] E. P. Pälvimäki, B. L. Roth, H. Majasuo, et al., “Interactions of Selective Serotonin Reuptake Inhibitors With the Serotonin 5-HT2c Receptor,” Psychopharmacology 126, no. 3 (1996): 234-240.

[176] K. D. Alex and E. A. Pehek, “Pharmacologic Mechanisms of Serotonergic Regulation of Dopamine Neurotransmission,” Pharmacology & Therapeutics 113, no. 2 (2007): 296-320.

[177] M. J. Millan, F. Lejeune, and A. Gobert, “Reciprocal Autoreceptor and Heteroreceptor Control of Serotonergic, Dopaminergic and Noradrenergic Transmission in the Frontal Cortex: Relevance to the Actions of Antidepressant Agents,” Journal of Psychopharmacology 14, no. 2 (2000): 114-138.

[178] J. Cavaillé, K. Buiting, M. Kiefmann, et al., “Identification of Brain-specific and Imprinted Small Nucleolar RNA Genes Exhibiting an Unusual Genomic Organization,” PNAS 97, no. 26 (2000): 14311-14316.

[179] C. A. Castellani, B. I. Laufer, M. G. Melka, E. J. Diehl, R. L. O'Reilly, and S. M. Singh, “DNA Methylation Differences in Monozygotic Twin Pairs Discordant for Schizophrenia Identifies Psychosis Related Genes and Networks,” BMC Medical Genomics 8 (2015): 17.

[180] R. Lin, H. Mitsuhashi, L. M. Fiori, et al., “SNORA69 is Up-regulated in the Lateral Habenula of Individuals With Major Depressive Disorder,” Scientific Reports 14, no. 1 (2024): 8258.

[181] E. Bieth, S. Eddiry, V. Gaston, et al., “Highly Restricted Deletion of the SNORD116 Region Is Implicated in Prader-Willi Syndrome,” European Journal of Human Genetics 23, no. 2 (2015): 252-255.

[182] Q. Tan, K. J. Potter, L. C. Burnett, et al., “Prader-Willi-Like Phenotype Caused by an Atypical 15q11.2 Microdeletion,” Genes (Basel) 11, no. 2 (2020): 128.

[183] G. V. Lobacheva and G. V. Galaktionova, “State of the Organ of Vision and Behavior of Rats After Action on the Eye of Increased Doses of UV-irradiation],” Kosmicheskaia Biologiia I Aviakosmicheskaia Meditsina 24, no. 5 (1990): 48-51.

[184] A. Adhikari, N. A. Copping, B. Onaga, et al., “Cognitive Deficits in the Snord116 Deletion Mouse Model for Prader-Willi Syndrome,” Neurobiology of Learning and Memory 165 (2019): 106874.

[185] M. Falaleeva, J. Surface, M. Shen, P. de la Grange, and S. Stamm, “SNORD116 and SNORD115 Change Expression of Multiple Genes and Modify each Other's Activity,” Gene 572, no. 2 (2015): 266-273.

[186] Y. Xu, X. Xin, and T. Tao, “Decoding the Neurotoxic Effects of Propofol: Insights Into the RARα-Snhg1-Bdnf Regulatory Cascade,” American Journal of Physiology. Cell Physiology 326, no. 6 (2024): C1735-C1752.

[187] G. A. Roth, G. A. Mensah, and V. Fuster, “The Global Burden of Cardiovascular Diseases and Risks: A Compass for Global Action,” Journal of the American College of Cardiology 76, no. 25 (2020): 2980-2981.

[188] Y. Okugawa, Y. Toiyama, S. Toden, et al., “Clinical Significance of SNORA42 as an Oncogene and a Prognostic Biomarker in Colorectal Cancer,” Gut 66, no. 1 (2017): 107-117.

[189] J. E. O'Brien, N. Kibiryeva, X. G. Zhou, et al., “Noncoding RNA Expression in Myocardium From Infants With Tetralogy of Fallot,” Circulation: Cardiovascular Genetics 5, no. 3 (2012): 279-286.

[190] E. Mick, R. Shah, K. Tanriverdi, et al., “Stroke and Circulating Extracellular RNAs,” Stroke; A Journal of Cerebral Circulation 48, no. 4 (2017): 828-834.

[191] K. E. J. Håkansson, E. A. C. Goossens, S. Trompet, et al., “Genetic Associations and Regulation of Expression Indicate an Independent Role for 14q32 snoRNAs in human Cardiovascular Disease,” Cardiovascular Research 115, no. 10 (2019): 1519-1532.

[192] C. I. Michel, C. L. Holley, B. S. Scruggs, et al., “Small Nucleolar RNAs U32a, U33, and U35a Are Critical Mediators of Metabolic Stress,” Cell Metabolism 14, no. 1 (2011): 33-44.

[193] E. Z. Amri and M. Scheideler, “Small Non Coding RNAs in Adipocyte Biology and Obesity,” Molecular and Cellular Endocrinology 456 (2017): 87-94.

[194] J. E. Schaffer, “Death by Lipids: The Role of Small Nucleolar RNAs in Metabolic Stress,” Journal of Biological Chemistry 295, no. 25 (2020): 8628-8635.

[195] C. L. Holley, M. W. Li, B. S. Scruggs, S. J. Matkovich, D. S. Ory, and J. E. Schaffer, “Cytosolic Accumulation of Small Nucleolar RNAs (snoRNAs) Is Dynamically Regulated by NADPH Oxidase,” Journal of Biological Chemistry 290, no. 18 (2015): 11741-11748.

[196] A. C. Sletten, J. W. Davidson, B. Yagabasan, et al., “Loss of SNORA73 Reprograms Cellular Metabolism and Protects Against Steatohepatitis,” Nature Communications 12, no. 1 (2021): 5214.

[197] A. Ogren, N. Kibiryeva, J. Marshall, J. E. O'Brien, and D. C. Bittel, “Snord94 expression Level Alters Methylation at C62 in snRNA U6,” PLoS ONE 14, no. 12 (2019): e0226035.

[198] L. Yin, Y. Tang, and M. Jiang, “Research on the Circular RNA Bioinformatics in Patients With Acute Myocardial Infarction,” Journal of Clinical Laboratory Analysis 35, no. 2 (2021): e23621.

[199] G. J. Schena, E. K. Murray, A. N. Hildebrand, et al., “Cortical Bone Stem Cell-derived Exosomes' therapeutic Effect on Myocardial Ischemia-reperfusion and Cardiac Remodeling,” American Journal of Physiology. Heart and Circulatory Physiology 321, no. 6 (2021): H1014-H1029.

[200] S. M. Welten, E. A. Goossens, P. H. Quax, and A. Y. Nossent, “The Multifactorial Nature of microRNAs in Vascular Remodelling,” Cardiovascular Research 110, no. 1 (2016): 6-22.

[201] E. van Ingen, D. A. L. van den Homberg, M. L. van der Bent, et al., “C/D Box snoRNA SNORD113-6/AF357425 Plays a Dual Role in Integrin Signalling and Arterial Fibroblast Function via Pre-mRNA Processing and 2'O-ribose Methylation,” Human Molecular Genetics 31, no. 7 (2022): 1051-1066.

[202] E. van Ingen, P. A. M. Engbers, T. Woudenberg, et al., “C/D Box snoRNA SNORD113-6 Guides 2'-O-methylation and Protects Against Site-specific Fragmentation of tRNA(Leu)(TAA) in Vascular Remodeling,” Molecular Therapy Nucleic Acids 30 (2022): 162-172.

[203] W. R. Hiatt and J. Goldstone, “Atherosclerotic Peripheral Vascular Disease Symposium II: Nomenclature for Vascular Diseases,” Circulation 118, no. 25 (2008): 2826-2829.

[204] U. Campia, M. Gerhard-Herman, G. Piazza, and S. Z. Goldhaber, “Peripheral Artery Disease: Past, Present, and Future,” American Journal of Medicine 132, no. 10 (2019): 1133-1141.

[205] K. E. J. Håkansson, O. Sollie, K. H. Simons, P. H. A. Quax, J. Jensen, and A. Y. Nossent, “Circulating Small Non-coding RNAs as Biomarkers for Recovery after Exhaustive or Repetitive Exercise,” Frontiers in Physiology 9 (2018): 1136.

[206] A. Y. Nossent, N. Ektefaie, J. Wojta, et al., “Plasma Levels of snoRNAs Are Associated With Platelet Activation in Patients With Peripheral Artery Disease,” International Journal of Molecular Sciences 20, no. 23 (2019): 5975.

[207] M. Y. Desai, A. Owens, and A. Wang, “Medical Therapies for Hypertrophic Cardiomyopathy: Current state of the Art,” Progress in Cardiovascular Diseases 80 (2023): 32-37.

[208] V. James, Z. A. Nizamudeen, D. Lea, et al., “Transcriptomic Analysis of Cardiomyocyte Extracellular Vesicles in Hypertrophic Cardiomyopathy Reveals Differential snoRNA Cargo,” Stem Cells and Development 30, no. 24 (2021): 1215-1227.

[209] C. A. Tallo, L. H. Duncan, A. H. Yamamoto, et al., “Heat Shock Proteins and Small Nucleolar RNAs Are Dysregulated in a Drosophila Model for Feline Hypertrophic Cardiomyopathy,” G3 Genes|Genomes|Genetics 11, no. 1 (2021): kaa014.

[210] N. S. Lai, H. C. Yu, K. Y. Huang, C. H. Tung, H. B. Huang, and M. C. Lu, “Decreased T Cell Expression of H/ACA Box Small Nucleolar RNA 12 Promotes Lupus Pathogenesis in Patients With Systemic Lupus Erythematosus,” Lupus 27, no. 9 (2018): 1499-1508.

[211] F. G. Lafaille, O. Harschnitz, Y. S. Lee, et al., “Human SNORA31 Variations Impair Cortical Neuron-intrinsic Immunity to HSV-1 and Underlie herpes Simplex Encephalitis,” Nature Medicine 25, no. 12 (2019): 1873-1884.

[212] M. M. Steinbusch, Y. Fang, P. I. Milner, et al., “Serum snoRNAs as Biomarkers for Joint Ageing and Post Traumatic Osteoarthritis,” Scientific Reports 7 (2017): 43558.

[213] M. J. Peffers, A. Chabronova, P. Balaskas, et al., “SnoRNA Signatures in Cartilage Ageing and Osteoarthritis,” Scientific Reports 10, no. 1 (2020): 10641.

[214] E. G. J. Ripmeester, M. M. J. Caron, G. G. H. van den Akker, et al., “Impaired Chondrocyte U3 snoRNA Expression in Osteoarthritis Impacts the Chondrocyte Protein Translation Apparatus,” Scientific Reports 10, no. 1 (2020): 13426.

[215] A. Parray, F. A. Mir, A. Doudin, et al., “SnoRNAs and miRNAs Networks Underlying COVID-19 Disease Severity,” Vaccines (Basel) 9, no. 10 (2021): 1056.

[216] D. Ma, X. Zhou, Y. Wang, et al., “Changes in the Small Noncoding RNAome during M1 and M2 Macrophage Polarization,” Frontiers in immunology 13 (2022): 799733.

[217] F. Xiao, J. Peng, Y. Li, et al., “Small Noncoding RNAome Changes during Human Bone Marrow Mesenchymal Stem Cells Senescence in Vitro,” Frontiers in Endocrinology 13 (2022): 808223.

[218] M. W. Painter, S. Davis, R. R. Hardy, D. Mathis, and C. Benoist, “Transcriptomes of the B and T Lineages Compared by Multiplatform Microarray Profiling,” Journal of Immunology 186, no. 5 (2011): 3047-3057.

[219] J. M. Toung, M. Morley, M. Li, and V. G. Cheung, “RNA-sequence Analysis of human B-cells,” Genome Research 21, no. 6 (2011): 991-998.

[220] H. Brüünsgaard and B. K. Pedersen, “Age-related Inflammatory Cytokines and Disease,” Immunology and Allergy Clinics of North America 23, no. 1 (2003): 15-39.

[221] D. E. L. Promislow, “A Geroscience Perspective on COVID-19 Mortality,” Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 75, no. 9 (2020): e30-e33.

[222] A. K. Simon, G. A. Hollander, and A. McMichael, “Evolution of the Immune System in Humans From Infancy to Old Age,” Proceedings of the Royal Society B Biological Sciences 282, no. 1821 (2015): 20143085.

[223] D. K. Dunn-Walters, “The Ageing human B Cell Repertoire: A Failure of Selection?,” Clinical and Experimental Immunology 183, no. 1 (2016): 50-56.

[224] R. L. Baudier, K. J. Zwezdaryk, M. Czarny-Ratajczak, L. H. Kodroff, D. E. Sullivan, and E. B. Norton, “Unique Transcriptome Changes in Peripheral B Cells Revealed by Comparing Age Groups from Naive or Vaccinated Mice, Including snoRNA and Cdkn2a,” Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 75, no. 12 (2020): 2326-2332.

[225] Y. Cheng, S. Wang, H. Zhang, et al., “A Non-canonical Role for a Small Nucleolar RNA in Ribosome Biogenesis and Senescence,” Cell 187, no. 17 (2024): 4770-4789.

[226] J. C. Wiegard, M. A. C. Schlüter, O. Y. Burenina, et al. Northern Blot Detection of Tiny RNAs. In: Rederstorff M, ed. “Small Non-Coding RNAs: Methods and Protocols” (US: Springer, 2021): 41-58.

[227] T. Blevins. Northern Blotting Techniques for Small RNAs. In: Kovalchuk I, Zemp FJ, eds. “Plant Epigenetics: Methods and Protocols”. (Humana Press, 2010): 87-107.

[228] Q. Huang, Z. Mao, S. Li, J. Hu, and Y. Zhu, “A Non-radioactive Method for Small RNA Detection by northern Blotting,” Rice 7, no. 1 (2014): 26.

[229] E. Varkonyi-Gasic and R. P. Hellens. qRT-PCR of Small RNAs. In: Kovalchuk I, Zemp FJ, eds. “Plant Epigenetics: Methods and Protocols”. (Humana Press, 2010): 109-122.

[230] P. Zayakin, “sRNAflow: A Tool for the Analysis of Small RNA-Seq Data,” Non-Coding RNA 10, no. 1 (2024): 6.

[231] C. Dard-Dascot, D. Naquin, Y. d'Aubenton-Carafa, K. Alix, C. Thermes, and E. van Dijk, “Systematic Comparison of Small RNA Library Preparation Protocols for next-generation Sequencing,” BMC Genomics [Electronic Resource] 19, no. 1 (2018): 118.

[232] C. Lu, Y. Wei, X. Wang, et al., “DNA-methylation-mediated Activating of lncRNA SNHG12 Promotes Temozolomide Resistance in Glioblastoma,” Molecular Cancer 19, no. 1 (2020): 28.

[233] N. Barbezier, G. Canino, J. Rodor, et al., “Processing of a Dicistronic tRNA-snoRNA Precursor: Combined Analysis in Vitro and in Vivo Reveals Alternate Pathways and Coupling to Assembly of snoRNP,” Plant Physiology 150, no. 3 (2009): 1598-1610.

[234] T. Bratkovič, J. Božič, and B. Rogelj, “Functional Diversity of Small Nucleolar RNAs,” Nucleic Acids Research 48, no. 4 (2019): 1627-1651.

[235] J. E. Heraud-Farlow, T. Sharangdhar, and M. A. Kiebler. Fluorescent in Situ Hybridization in Primary Hippocampal Neurons to Detect Localized mRNAs. In: Hauptmann G, ed. “In Situ Hybridization Methods” (New York: Springer, 2015): 321-337.

[236] V. Marchand, L. Ayadi, A. El Hajj, F. Blanloeil-Oillo, M. Helm, and Y. Motorin, “High-Throughput Mapping of 2'-O-Me Residues in RNA Using Next-Generation Sequencing (Illumina RiboMethSeq Protocol),” Methods in Molecular Biology 1562 (2017): 171-187.

[237] T. M. Carlile, M. F. Rojas-Duran, B. Zinshteyn, H. Shin, K. M. Bartoli, and W. V. Gilbert, “Pseudouridine Profiling Reveals Regulated mRNA Pseudouridylation in Yeast and human Cells,” Nature 515, no. 7525 (2014): 143-146.

[238] H. Kobayashi and R. H. Singer, “Single-molecule Imaging of microRNA-mediated Gene Silencing in Cells,” Nature Communications 13, no. 1 (2022): 1435.

[239] B. Liu, T. Wu, B. A. Miao, et al., “snoRNA-facilitated Protein Secretion Revealed by Transcriptome-wide snoRNA Target Identification,” Cell 188, no. 2 (2025): 465-483.

[240] B. Liu, “Mapping snoRNA Targets Transcriptome-Wide With snoKARR-seq,” Acs Chemical Biology 20, no. 2 (2025): 242-244.

[241] M. Helm, A. Y. Kobitski, and G. U. Nienhaus, “Single-molecule Förster Resonance Energy Transfer Studies of RNA Structure, Dynamics and Function,” Biophysical Reviews 1, no. 4 (2009): 161.

[242] R. B. Denman, “Using RNAFOLD to Predict the Activity of Small Catalytic RNAs,” Biotechniques 15, no. 6 (1993): 1090-1095.

[243] M. Zuker, “Mfold Web Server for Nucleic Acid Folding and Hybridization Prediction,” Nucleic Acids Research 31, no. 13 (2003): 3406-3415.

[244] S. A. Mortimer, C. Trapnell, S. Aviran, L. Pachter, and J. B. Lucks, “SHAPE-Seq: High-Throughput RNA Structure Analysis,” Current Protocols in Chemical Biology 4, no. 4 (2012): 275-297.

[245] N. Chakravorty, “Non-coding RNAs: The Silent Regulators of Health and Diseases,” Molecular Biology Reports 49, no. 7 (2022): 6971-6973.

[246] P. Darren Mathurin-St-Pierre, Clement Desjardins-Henri. snoDB Version 1.2.1. Accessed May 13, 2025, http://scottgroup.med.usherbrooke.ca/snoDB/.

[247] D. Bergeron, H. Paraqindes, É. Fafard-Couture, et al., “snoDB 2.0: An Enhanced Interactive Database, Specializing in human snoRNAs,” Nucleic Acids Research (2025), https://bioinfo-scottgroup.med.usherbrooke.ca/snoDB/.

[248] M. J. Ken Nakatsu, V. Khadka, M. Nasu, and Y. Deng, “sRNAfrag: A Pipeline and Suite of Tools to Analyze Fragmentation in Small RNA Sequencing Data,” Briefings in Bioinformatics (2024), Accessed May 13, 2025, https://doi.org/10.1093/bib/bbad515.

[249] G. C. S. Deschamps-Francoeur, S. Abou-Elela, and M. S. Scott, “The snoGloBe Interaction Predictor Reveals a Broad Spectrum of C/D snoRNA RNA Targets,” BioRxiv (2021), Accessed May 13, 2025, https://www.biorxiv.org/content/10.1101/2021.09.14.460265v3.

[250] W. Zhang and B. Liu, “iSnoDi-MDRF:Identifying snoRNA-disease Associations Based on Multiple Biological Data by Ranking Framework,” IEEE/ACM Transactions on Computational Biology and Bioinformatics 20, no. 5 (2023): 3013-3019, Accessed May 13, 2025, http://bliulab.net/iSnoDi-MDRF/home/.

[251] W. Zhang and B. Liu, “iSnoDi-MDRF: Identifying snoRNA-Disease Associations Based on Multiple Biological Data by Ranking Framework,” IEEE/ACM Trans Comput Biol Bioinform 20, no. 5 (2023): 3013-3019.

[252] K. Nakatsu, M. Jijiwa, V. Khadka, M. Nasu, and Y. Deng, “sRNAfrag: A Pipeline and Suite of Tools to Analyze Fragmentation in Small RNA Sequencing Data,” Brief Bioinform 25, no. 1 (2023): bbad515.

[253] A. Sklias, S. Cruciani, V. Marchand, et al., “Comprehensive Map of Ribosomal 2'-O-methylation and C/D Box snoRNAs in Drosophila Melanogaster,” Nucleic Acids Research 52, no. 6 (2024): 2848-2864.

[254] I. Kalvari, E. P. Nawrocki, J. Argasinska, et al., “Non-Coding RNA Analysis Using the Rfam Database,” CP in Bioinformatics 62, no. 1 (2018): e51.

[255] M. Yoshihama, A. Nakao, and N. Kenmochi, “snOPY: A Small Nucleolar RNA Orthological Gene Database,” BMC Research Res Notes 6 (2013): 426.

[256] N. F. Fitz, J. Wang, M. I. Kamboh, R. Koldamova, and I. Lefterov, “Small Nucleolar RNAs in Plasma Extracellular Vesicles and Their Discriminatory Power as Diagnostic Biomarkers of Alzheimer's Disease,” Neurobiology of Disease 159 (2021): 105481.

[257] P. Zayakin, L. Sadovska, K. Eglītis, et al., “Extracellular Vesicles-A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies,” Cancers (Basel) 15, no. 17 (2023): 4329.

[258] T. A. P. Driedonks, S. G. van der Grein, Y. Ariyurek, et al., “Immune Stimuli Shape the Small Non-coding Transcriptome of Extracellular Vesicles Released by Dendritic Cells,” Cellular and Molecular Life Sciences 75, no. 20 (2018): 3857-3875.

[259] B. Cheng. Circulating Extracellular Exosomal Small RNA as Potential Biomarker for Human Pancreatic Cancer. 2020. Accessed May 13, 2025. https://clinicaltrials.gov/study/NCT04636788.

[260] Study Details | Circulating Extracellular Exosomal Small RNA as Potential Biomarker for Human Pancreatic Cancer | ClinicalTrials.gov.

[261] Study Details | Transcripts with Retained H/ACA Box SnoRNA Sequences As Biomarkers for Estrogen Dependence in Lum-B Breast Carcinomas | ClinicalTrials.gov.

[262] Study Details | SNORD3A IN ISCHEMIC HEART DISEASE AND HEART FAILURE | ClinicalTrials.gov.

[263] M. Pace, I. Colombi, M. Falappa, et al., “Loss of Snord116 Alters Cortical Neuronal Activity in Mice: A Preclinical Investigation of Prader-Willi Syndrome,” Human Molecular Genetics 29, no. 12 (2020): 2051-2064.

[264] G. Lassi, S. Maggi, E. Balzani, I. Cosentini, C. Garcia-Garcia, and V. Tucci, “Working-for-Food Behaviors: A Preclinical Study in Prader-Willi Mutant Mice,” Genetics 204, no. 3 (2016): 1129-1138.

[265] M. R. Pickard and G. T. Williams, “Regulation of Apoptosis by Long Non-coding RNA GAS5 in Breast Cancer Cells: Implications for Chemotherapy,” Breast Cancer Research and Treatment 145, no. 2 (2014): 359-370 Ideue T, Hino K, Kitao S, Yokoi T, Hirose T. Efficient oligonucleotide-mediated degradation of nuclear noncoding RNAs in mammalian cultured cells. Rna. Aug 2009;15(8): 1578-87.

[266] X. H. Liang, T. A. Vickers, S. Guo, and S. T. Crooke, “Efficient and Specific Knockdown of Small Non-coding RNAs in Mammalian Cells and in Mice,” Nucleic Acids Research 39, no. 3 (2011): e13.

[267] T. Ideue, K. Hino, S. Kitao, T. Yokoi, and T. Hirose, “Efficient Oligonucleotide-mediated Degradation of Nuclear Noncoding RNAs in Mammalian Cultured Cells,” Rna 15, no. 8 (2009): 1578-1587.

[268] H. J. Bao, X. Chen, X. Liu, et al., “Box C/D snoRNA SNORD89 Influences the Occurrence and Development of Endometrial Cancer Through 2'-O-methylation Modification of Bim,” Cell Death Discovery 8, no. 1 (2022): 309.

[269] Q. Li, B. Xie, X. Chen, et al., “SNORD6 promotes Cervical Cancer Progression by Accelerating E6-mediated p53 Degradation,” Cell Death Discovery 9, no. 1 (2023): 192.

[270] S. Karaki, C. Paris, and P. Rocchi, Antisense Oligonucleotides, a Novel Developing Targeting Therapy. (Antisense Therapy, 2019).

[271] S. Li, H. Zhao, J. Li, A. Zhang, and H. Wang, “Downregulation of Long Non-coding RNA LET Predicts Poor Prognosis and Increases Notch Signaling in Non-small Cell Lung Cancer,” Oncotarget 9, no. 1 (2018): 1156-1168.

[272] X. Ruan, P. Li, A. Cangelosi, L. Yang, and H. Cao, “A Long Non-coding RNA, lncLGR, Regulates Hepatic Glucokinase Expression and Glycogen Storage During Fasting,” Cell reports 14, no. 8 (2016): 1867-1875.

[273] Q. Yu, Y. Qiu, X. Wang, et al., “Efficient siRNA Transfer to Knockdown a Placenta Specific lncRNA Using RGD-modified Nano-liposome: A New Preeclampsia-Like Mouse Model,” International Journal of Pharmaceutics 546, no. 1-2 (2018): 115-124.

[274] L. Chang, G. Wang, T. Jia, et al., “Armored Long Non-coding RNA MEG3 Targeting EGFR Based on Recombinant MS2 Bacteriophage Virus-Like Particles Against Hepatocellular Carcinoma,” Oncotarget 7, no. 17 (2016): 23988-24004.

[275] Z. C. Zhang, C. Tang, Y. Dong, J. Zhang, T. Yuan, and X. L. Li, “Targeting LncRNA-MALAT1 Suppresses the Progression of Osteosarcoma by Altering the Expression and Localization of β-catenin,” Journal of Cancer 9, no. 1 (2018): 71-80.

[276] J. Yang, “Patisiran for the Treatment of Hereditary Transthyretin-mediated Amyloidosis,” Expert Review of Clinical Pharmacology 12, no. 2 (2019): 95-99.

[277] Q. Guo, X. Zheng, P. Yang, et al., “Small Interfering RNA Delivery to the Neurons near the Amyloid Plaques for Improved Treatment of Alzheimer׳s Disease,” Acta Pharmaceutica Sinica B 9, no. 3 (2019): 590-603.

[278] N. Gong, X. Teng, J. Li, and X. J. Liang, “Antisense Oligonucleotide-Conjugated Nanostructure-Targeting lncRNA MALAT1 Inhibits Cancer Metastasis,” ACS Appl Mater Interfaces 11, no. 1 (2019): 37-42.

[279] H. Q. Song, W. Pan, R. Q. Li, et al., “Rodlike Supramolecular Nanoassemblies of Degradable Poly(Aspartic Acid) Derivatives and Hydroxyl-Rich Polycations for Effective Delivery of Versatile Tumor-Suppressive ncRNAs,” Small 14, no. 9 (2018): 1703152.

[280] C. Wang, S. Li, B. Qian, et al., “AIEgen-functionalized Nanoprobes and Nanomedicines for Cancer Diagnosis and Therapy,” Coordination Chemistry Reviews 520 (2024): 216148.

[281] R. Liu, C. Luo, Z. Pang, et al., “Advances of Nanoparticles as Drug Delivery Systems for Disease Diagnosis and Treatment,” Chinese Chemical Letters 34, no. 2 (2023): 107518.

[282] Y. Ma, S. Li, X. Lin, and Y. Chen, “A Perspective of Lipid Nanoparticles for RNA Delivery,” Exploration 4 (2024): 20230147.

[283] L. Gao, J. Fan, J. He, X. Che, X. Wang, and C. Han, “Small Nucleolar RNAs as Diagnostic and Prognostic Biomarkers in Cancer: A Systematic Review and Meta-Analysis,” Technology in Cancer Research & Treatment 23 (2024): 15330338241245939.

[284] Y. Kargapolova, M. Levin, K. Lackner, and S. Danckwardt, “sCLIP-an Integrated Platform to Study RNA-protein Interactomes in Biomedical Research: Identification of CSTF2tau in Alternative Processing of Small Nuclear RNAs,” Nucleic Acids Research 45, no. 10 (2017): 6074-6086.

[285] T. S. Rozhdestvensky, T. H. Tang, I. V. Tchirkova, J. Brosius, J. P. Bachellerie, and A. Hüttenhofer, “Binding of L7Ae Protein to the K-turn of Archaeal snoRNAs: A Shared RNA Binding Motif for C/D and H/ACA Box snoRNAs in Archaea,” Nucleic Acids Research 31, no. 3 (2003): 869-877.

[286] H. Ginisty, F. Amalric, and P. Bouvet, “Nucleolin Functions in the First Step of Ribosomal RNA Processing,” Embo Journal 17, no. 5 (1998): 1476-1486.

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