Gold glitters everywhere: nucleus microRNAs and their functions

Abstract

As a highly conserved class of endogenous small (~22 nucleotides) non-coding RNAs, microRNAs (miRNAs) regulate a broad spectrum of biological processes. Increasing evidences suggested that miRNAs generally regulated gene expression at the posttranscriptional stage via inhibiting the translational process or degrading mRNA. Recent studies have also revealed that there is extensive amount of miRNA, as well as miRNA function-related proteins, in the cell nucleus. Although the molecular basis underneath the biogenesis and function of nucleus miRNAs remains largely unknown, the presence of various miRNAs and miRNA function-related proteins in the nucleus strongly argue that miRNAs may execute their role throughout the whole gene expression pathway. Here we review the recent advances in the researches about the nucleus miRNAs, including the biosynthesis pathways, biological functions and potential regulation machinery of nucleus miRNAs.

Keywords

nucleus miRNA / nucleus RISC / Argonaute family / Exportins / nucleus-cytoplasm shutting / gene regulatory network

References

[1] Ambros V (2004). The functions of animal microRNAs. Nature, 431(7006): 350–355

[2] Bartel D P (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116(2): 281–297

[3] Berezhna S Y, Supekova L, Supek F, Schultz P G, Deniz A A (2006). siRNA in human cells selectively localizes to target RNA sites. Proc Natl Acad Sci USA, 103(20): 7682–7687

[4] Castanotto D, Lingeman R, Riggs A D, Rossi J J (2009). CRM1 mediates nuclear-cytoplasmic shuttling of mature microRNAs. Proc Natl Acad Sci USA, 106(51): 21655–21659

[5] Emmerth S, Schober H, Gaidatzis D, Roloff T, Jacobeit K, Bühler M (2010). Nuclear retention of fission yeast dicer is a prerequisite for RNAi-mediated heterochromatin assembly. Dev Cell, 18(1): 102–113

[6] Földes-Papp Z, König K, Studier H, Bückle R, Breunig H G, Uchugonova A, Kostner G M (2009). Trafficking of mature miRNA-122 into the nucleus of live liver cells. Curr Pharm Biotechnol, 10(6): 569–578

[7] Fukagawa T, Nogami M, Yoshikawa M, Ikeno M, Okazaki T, Takami Y, Nakayama T, Oshimura M (2004). Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat Cell Biol, 6(8): 784–791

[8] Guang S, Bochner A F, Pavelec D M, Burkhart K B, Harding S, Lachowiec J, Kennedy S (2008). An Argonaute transports siRNAs from the cytoplasm to the nucleus. Science, 321(5888): 537–541

[9] Hwang H W, Wentzel E A, Mendell J T (2007). A hexanucleotide element directs microRNA nuclear import. Science, 315(5808): 97–100

[10] Janowski B A, Huffman K E, Schwartz J C, Ram R, Nordsell R, Shames D S, Minna J D, Corey D R (2006). Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nat Struct Mol Biol, 13(9): 787–792

[11] Janowski B A, Younger S T, Hardy D B, Ram R, Huffman K E, Corey D R (2007). Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol, 3(3): 166–173

[12] Jeffries C D, Fried H M, Perkins D O (2010). Additional layers of gene regulatory complexity from recently discovered microRNA mechanisms. Int J Biochem Cell Biol, 42(8): 1236–1242

[13] Kawasaki H, Taira K (2004). Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature, 431(7005): 211–217

[14] Kim D H, Saetrom P, Snøve O Jr, Rossi J J (2008). MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci USA, 105(42): 16230–16235

[15] Li L C, Okino S T, Zhao H, Pookot D, Place R F, Urakami S, Enokida H, Dahiya R (2006). Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci USA, 103(46): 17337–17342

[16] Liao J Y, Ma L M, Guo Y H, Zhang Y C, Zhou H, Shao P, Chen Y Q, Qu L H, Xu S (2010). Deep sequencing of human nuclear and cytoplasmic small RNAs reveals an unexpectedly complex subcellular distribution of miRNAs and tRNA 3' trailers. PLoS ONE, 5(5): e10563

[17] Lund E, Güttinger S, Calado A, Dahlberg J E, Kutay U (2004). Nuclear export of microRNA precursors. Science, 303(5654): 95–98

[18] Marcon E, Babak T, Chua G, Hughes T, Moens P B (2008). miRNA and piRNA localization in the male mammalian meiotic nucleus. Chromosome Res, 16(2): 243–260

[19] Meister G, Landthaler M, Dorsett Y, Tuschl T (2004a). Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA, 10(3): 544–550

[20] Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004b). Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell, 15(2): 185–197

[21] Noto T, Kurth H M, Kataoka K, Aronica L, DeSouza L V, Siu K W, Pearlman R E, Gorovsky M A, Mochizuki K (2010). The Tetrahymena argonaute-binding protein Giw1p directs a mature argonaute-siRNA complex to the nucleus. Cell, 140(5): 692–703

[22] Ohrt T, Mütze J, Staroske W, Weinmann L, Höck J, Crell K, Meister G, Schwille P (2008). Fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy reveal the cytoplasmic origination of loaded nuclear RISC in vivo in human cells. Nucleic Acids Res, 36(20): 6439–6449

[23] Okada C, Yamashita E, Lee S J, Shibata S, Katahira J, Nakagawa A, Yoneda Y, Tsukihara T (2009). A high-resolution structure of the pre-microRNA nuclear export machinery. Science, 326(5957): 1275–1279

[24] Onodera Y, Haag J R, Ream T, Nunes P C, Pontes O, Pikaard C S (2005). Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell, 120(5): 613–622

[25] Pal-Bhadra M, Leibovitch B A, Gandhi S G, Rao M, Bhadra U, Birchler J A, Elgin S C (2004). Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science, 303(5658): 669–672

[26] Place R F, Li L C, Pookot D, Noonan E J, Dahiya R (2008). MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA, 105(5): 1608–1613

[27] Politz J C, Hogan E M, Pederson T (2009). MicroRNAs with a nucleolar location. RNA, 15(9): 1705–1715

[28] Politz J C, Zhang F, Pederson T (2006). MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells. Proc Natl Acad Sci USA, 103(50): 18957–18962

[29] Robb G B, Brown K M, Khurana J, Rana T M (2005). Specific and potent RNAi in the nucleus of human cells. Nat Struct Mol Biol, 12(2): 133–137

[30] Shibata S, Sasaki M, Miki T, Shimamoto A, Furuichi Y, Katahira J, Yoneda Y (2006). Exportin-5 orthologues are functionally divergent among species. Nucleic Acids Res, 34(17): 4711–4721

[31] Volpe T A, Kidner C, Hall I M, Teng G, Grewal S I, Martienssen R A (2002). Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science, 297(5588): 1833–1837

[32] Wassenegger M, Heimes S, Riedel L, Sänger H L (1994). RNA-directed de novo methylation of genomic sequences in plants. Cell, 76(3): 567–576

[33] Weinmann L, Höck J, Ivacevic T, Ohrt T, Mütze J, Schwille P, Kremmer E, Benes V, Urlaub H, Meister G (2009). Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell, 136(3): 496–507

[34] Winter J, Jung S, Keller S, Gregory R I, Diederichs S (2009). Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol, 11(3): 228–234

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg