The perinucleolar compartment associates with malignancy

Abstract

The perinucleolar compartment (PNC) is a unique nuclear substructure, forming predominantly in cancer cells both in vitro and in vivo. PNC prevalence (percentage of cells containing at least one PNC) has been found to positively correlate with disease progression in several cancers (breast, ovarian, and colon). While there is a clear association between PNCs and cancer, the molecular function of the PNC remains unclear. Here we summarize the current understanding of the association of PNCs with cancer and its possible functions in cancer cells.

Keywords

PNC / cancer / nuclear substructure / gene expression regulation / structure and function

References

[1] Altman S (1990). Ribonuclease P. Postscript. J Biol Chem, 265(33): 20053-20056

[2] Anderson J T, Wilson S M, (1993). NAB2: a yeast nuclear polyadenylated RNA-binding protein essential for cell viability. Mol Cell Biol, 13(5): 2730-2741

[3] Apponi L H, Corbett A H, Pavlath G K (2011). RNA-binding proteins and gene regulation in myogenesis. Trends Pharmacol Sci, 32(11): 652-658

[4] Bond C S, Fox A H (2009). Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol, 186(5): 637-644

[5] Castelo-Branco P, Furger A, Wollerton M, Smith C, Moreira A, Proudfoot N (2004). Polypyrimidine tract binding protein modulates efficiency of polyadenylation. Mol Cell Biol, 24(10): 4174-4183

[6] Charlet B N, Savkur R S, Singh G, Philips A V, Grice E A, Cooper T A (2002). Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell, 10(1): 45-53

[7] Chen M, Zhang J, Manley J L (2010). Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA. Cancer Res, 70(22): 8977-8980

[8] Clayton D A (1994). A nuclear function for RNase MRP. Proc Natl Acad Sci USA, 91(11): 4615-4617

[9] Esakova O, Krasilnikov A S (2010). Of proteins and RNA: the RNase P/MRP family. RNA, 16(9): 1725-1747

[10] Esakova O, Perederina A, Quan C, Berezin I, Krasilnikov A S (2011). Substrate recognition by ribonucleoprotein ribonuclease MRP. RNA, 17(2): 356-364

[11] Fox A H, Lamond A I (2010). Paraspeckles. Cold Spring Harb Perspect Biol, 2(7): a000687

[12] Frank R, Hargreaves R (2003). Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov, 2(7): 566-580

[13] Ghetti A, Pinol-Roma S, Michael W M, Morandi C, Dreyfuss G (1992). hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs. Nucleic Acids Res, 20(14): 3671-3678

[14] Gromak N, Rideau A, Southby J, Scadden A D J, Gooding C, Hüttelmaier S, Singer R H, Smith C W J (2003). The PTB interacting protein raver1 regulates alpha-tropomyosin alternative splicing. EMBO J, 22(23): 6356-6364

[15] Hall M P, Huang S, (2004). Differentiation-induced colocalization of the KH-type splicing regulatory protein with polypyrimidine tract binding protein and the c-src pre-mRNA. Mol Biol Cell, 15(2): 774-786

[16] Hellen C U, Pestova T V, (1994). The cellular polypeptide p57 (pyrimidine tract-binding protein) binds to multiple sites in the poliovirus 5′ nontranslated region. J Virol, 68(2): 941-950

[17] Ho T H, Bundman D, Armstrong, D L, Cooper, T A (2005). Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy. Hum Mol Genet, 14(11): 1539-1547

[18] Huang S, Deerinck T J, Ellisman M H, Spector D L (1997). The dynamic organization of the perinucleolar compartment in the cell nucleus. J Cell Biol, 137(5): 965-974

[19] Huang S, Deerinck T J, Ellisman M H, Spector D L (1998). The perinucleolar compartment and transcription. J Cell Biol, 143(1): 35-47

[20] Huttelmaier S, Illenberger S, Grosheva I, Rudiger M, Singer R H, and Jockusch B M (2001). Raver1, a dual compartment protein, is a ligand for PTB/hnRNPI and microfilament attachment proteins. J Cell Biol, 155(5): 775-786

[21] Jackson D A, Hassan A B, Errington P R (1993). Visualization of focal sites of transcription within human nuclei. EMBO J, 12: 1059-1065

[22] Jacobson M R, Cao L G, Wang Y L, Pederson T (1995). Dynamic localization of RNase MRP RNA in the nucleolus observed by fluorescent RNA cytochemistry in living cells. J Cell Biol, 131(6 Pt 2): 1649-1658

[23] Jarrous N (2002). Human ribonuclease P: subunits, function, and intranuclear localization. RNA, 8(1): 1-7

[24] Jones K, Timchenko L, Timchenko N A (2012). The role of CUGBP1 in age-dependent changes of liver functions. Ageing Res Rev, 11(4): 442-449

[25] Kafasla P, Mickleburgh I, Llorian M, Coelho M, Gooding C, Cherny D, Joshi A, Kotik-Kogan O, Curry S, Eperon I C, Jackson R J, Smith C W J (2012). Defining the roles and interactions of PTB. Biochem Soc Trans, 40(4): 815-820

[26] Kamath R V, Leary D J, Huang S (2001). Nucleocytoplasmic shuttling of polypyrimidine tract-binding protein is uncoupled from RNA export. Mol Biol Cell, 12(12): 3808-3820

[27] Kamath R V, Thor A D, Wang C, Edgerton SM, Slusarczyk A, Leary D J, Wang J, Wiley E L, Jovanovic B, Wu Q, Nayar R, Kovarik P, Shi F, Huang S (2005). Perinucleolar compartment prevalence has an independent prognostic value for breast cancer. Cancer Res, 65(1): 246-253

[28] Kaminski A, Hunt S L, Patton J G, Jackson- Rna R J (1995). Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA. RNA, 1(9): 924-938

[29] Lee B, Matera A G, Ward D C, Craft J (1996). Association of RNase mitochondrial RNA processing enzyme with ribonuclease P in higher ordered structures in the nucleolus: a possible coordinate role in ribosome biogenesis. Proc Natl Acad Sci USA, 93(21): 11471-11476

[30] Liu Y, Norton J T, Witschi M A, Xu Q, Lou G, Wang C, H Appella D, Chen Z, Huang S (2011). Methoxyethylamino-numonafide is an efficacious and minimally toxic amonafide derivative in murine models of human cancer. Neoplasia, 13(5): 453-460

[31] Lou H, Gagel R F, Berget S M (1996). An intron enhancer recognized by splicing factors activates polyadenylation. Genes Dev, 10(2): 208-219

[32] Lou H, Helfman D M, Gagel R F, Berget S M (1999). Polypyrimidine tract-binding protein positively regulates inclusion of an alternative 3′-terminal exon. Mol Cell Biol, 19(1): 78-85

[33] Mahadevan M S (2012). Myotonic dystrophy: is a narrow focus obscuring the rest of the field? Curr Opin Neurol, 25(5): 609-613

[34] Matera A G, Frey M R, Margelot K, Wolin S L (1995). A perinucleolar compartment contains several RNA polymerase III transcripts as well as the polypyrimidine tract-binding protein, hnRNP I. J Cell Biol, 129(5): 1181-1193

[35] Norton J T, Pollock C B, Wang C, Schink J C, Kim J J, Huang S (2008). Perinucleolar compartment prevalence is a phenotypic pancancer marker of malignancy. Cancer, 113(4): 861-869

[36] Norton J T, Titus S A, Dexter D, Austin C P, Zheng W, Huang S (2009). Automated high-content screening for compounds that disassemble the perinucleolar compartment. J Biomol Screen, 14(9): 1045-1053

[37] Norton J T, Wang C, Gjidoda A, Henry R W, Huang S (2009). The perinucleolar compartment is directly associated with DNA. J Biol Chem, 284(7): 4090-4101

[38] Norton J T, Witschi M A, Luong L, Kawamura A, Ghosh S, Sharon Stack M, Sim E, Avram M J, Appella D H, Huang S (2008). Synthesis and anticancer activities of 6-amino amonafide derivatives. Anticancer Drugs, 19(1): 23-36

[39] O'Keefe R T, Mayeda A, Sadowski C L, Krainer A R, and Spec-tor D L (1994). Disruption of pre-mRNA splicing in vivo results in reorganization of splicing factors. J Cell Biol, 124(3): 249-260

[40] Paillard L, Legagneux V, Osborne H B (2003). A functional deadenylation assay identifies human CUG-BP as a deadenylation factor. Biol Cell, 95(2): 107-113

[41] Perederina A, Esakova O, Quan C, Khanova E, Krasilnikov A S (2010). Eukaryotic ribonucleases P/MRP: the crystal structure of the P3 domain. EMBO J, 29(4): 761-769

[42] Perez I, Lin C H, Mcafee J, Patton J (1997). Mutation of PTB binding sites causes misregulation of alternative 3′ splice site selection in vivo. RNA, 3(7): 764-778

[43] Pettaway C A, Pathak S, Greene G, Ramirez E, Wilson M R, Killion J J, Fidler I J (1996). Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res, 2(9): 1627-1636

[44] Pianese G (1896). Beitrag zur histologie und aetiologie der carcinoma. Histologische und experimentelle untersuchungen. Beitr Pathol Anat Allgem Pathol, 142(1): 193

[45] Pickering B M, Mitchell S A, Evans J R, Willis A E (2003). Polypyrimidine tract binding protein and poly r(C) binding protein 1 interact with the BAG-1 IRES and stimulate its activity in vitro and in vivo. Nucleic Acids Res, 31(2): 639-646

[46] Pollock C, Daily K, Nguyen V T, Wang C, Lewandowska M A, Bensaude O, Huang S (2011). Characterization of MRP RNA-protein interactions within the perinucleolar compartment. Mol Biol Cell, 22(6): 858-866

[47] Savkur R S, Philips A V, Cooper T A (2001). Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet, 29(1): 40-47

[48] Sawicka K, Bushell M, Spriggs K A, Willis A E (2008). Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein. Biochem Soc Trans, 36(Pt 4): 641-647

[49] Schneider R, Agol V I, Andino R, Bayard F, Cavener D R, Chappell S A, Chen J J, Darlix J L, Dasgupta A, Donze O (2001). New ways of initiating translation in eukaryotes. Mol Cell Biol, 21(23): 8238-8246

[50] Slusarczyk A, Kamath R, Wang C, Anchel D, Pollock C, Lewandowska M A, Fitzpatrick T, Bazett-Jones D P, Huang S (2010). Structure and function of the perinucleolar compartment in cancer cells. Cold Spring Harb Symp Quant Biol, 75(0): 599-605

[51] Steinberg T H, Burgess R R (1992). Tagetitoxin inhibition of RNA polymerase III transcription results from enhanced pausing at discrete sites and is template-dependent. J Biol Chem, 267(28): 20204-20211

[52] Steinberg T H, Mathews D E, Durbin R D, Burgess R R (1990). Tagetitoxin: a new inhibitor of eukaryotic transcription by RNA polymerase III. J Biol Chem, 265(1): 499-505

[53] Timchenko L T, Miller J W, Timchenko N A, DeVore D R, Datar K V, Lin L, Roberts R, Caskey C T, Swanson M S (1996). Identification of a (CUG)_n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res, 24(22): 4407-4414

[54] Valcarcel J, Gebauer F (1997). Post-transcriptional regulation: the dawn of PTB. Curr Biol, 7(11): R705-R708

[55] Van Eenennaam H, Vogelzangs J H, Lugtenberg D, Van Den Hoogen F H J, Van Venrooij W J, Pruijn G J M (2002). Identity of the RNase MRP- and RNase P-associated Th/To autoantigen. Arthritis Rheum, 46(12): 3266-3272

[56] Wagner E J, Carstens R P, Garcia-Blanco M A (1999). A novel isoform ratio switch of the polypyrimidine tract binding protein. Electrophoresis, 20(4-5): 1082-1086

[57] Wagner E J, Garcia-Blanco M A (2002). RNAi-mediated PTB depletion leads to enhanced exon definition. Mol Cell, 10(4): 943-949

[58] Wang C, Politz J C, Pederson T, Huang S (2003). RNA polymerase III transcripts and the PTB protein are essential for the integrity of the perinucleolar compartment. Mol Biol Cell, 14(6): 2425-2435

[59] Wansink D G, Schul W, van der Kraan I, van Steensel B, van Driel R, de Jong L (1993). Fluorescent labeling of nascent RNA reveals transcription by RNA polymerase II in domains scattered throughout the nucleus. J Cell Biol, 122(2): 283-293

[60] Witherell G W, Schultz-Witherell C S, Wimmer E C K A R D (1995). Cis-acting elements of the encephalomyocarditis virus internal ribosomal entry site. Virology, 214(2): 660-663

[61] Xiao S, Scott F, Fierke C A, Engelke D R (2002). EUKARYOTIC RIBONUCLEASE P: A Plurality of Ribonucleoprotein Enzymes. Annu Rev Biochem, 71(1): 165-189

[62] Xie J, Lee J A, Kress T L, Mowry K L, Black D L (2003). Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein. Proc Natl Acad Sci USA, 100(15): 8776-8781

[63] Zhang W, Liu H, Han K, Grabowski P J (2002). Region-specific alternative splicing in the nervous system: implications for regulation by the RNA-binding protein NAPOR. RNA, 8(5): 671-685

[64] Zwerger M, Ho C Y, Lammerding J (2011). Nuclear mechanics in disease. Annu Rev Biomed Eng, 13(1): 397-428

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg