Abstract
The perinucleolar compartment (PNC) is a nuclear substructure associated with, but structurally distinct from, the nucleolus. The PNC contains several RNA processing proteins and several RNA pol III transcripts, which form novel complexes. As determined by cell culture experiments and human tumor samples, the PNC forms exclusively in cancer cells and the percentage of cancer cells in a population that have one or more PNCs directly correlates with the malignancy of that population of cells. Therefore, the PNC is being developed as a prognostic marker for several malignancies. PNC elimination in cancer cells has proven to be a useful as screening method to discover probe compounds used to elucidate PNC biology and to discover compounds with the potential to be developed as minimally toxic anti-cancer drugs.
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References
Huang S, Deerinck TJ, Ellisman MH, Spector DL (1997) The dynamic organization of the perinucleolar compartment in the cell nucleus. J Cell Biol 137(5):965–974
Huang S, Deerinck TJ, Ellisman MH, Spector DL (1998) The perinucleolar compartment and transcription. J Cell Biol 143(1):35–47
Ghetti A, Piñol-Roma S, Michael WM, 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
Timchenko LT, Miller JW, Timchenko NA, DeVore DR, Datar KV, Lin L et al (1996) Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res 24:4407–4414
Hall MP, Huang S, Black DL (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
Hüttelmaier S, Illenberger S, Grosheva I, Rüdiger M, Singer RH, Jockusch BM (2001) Raver1, a dual compartment protein, is a ligand for PTB/hnRNPI and microfilament attachment proteins. J Cell Biol 155(5):775–786
Kleinhenz M, Fabienke S, Swiniarski N, Wittenmayer J, Kirsch B, Jockusch H et al (2005) Raver2, a new member of the hnRNP family. FEBS Lett 579(20):4254–4258
Shav-Tal Y, Lee BC, Bar-Haim S, Schori H, Zipori D (2001) Reorganization of nuclear factors during myeloid differentiation. J Cell Biochem 81:379–392
Lau PP, Chan L (2003) Involvement of a chaperone regulator, Bcl2-associated athanogene-4, in apolipoprotein B mRNA editing. J Biol Chem 278(52):52988–52996
Matera AG, Frey MR, Margelot K, Wolin SL (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
Wang C, Politz JC, 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 14:2425–2435
Pollock C, Daily K, Nguyen VT, Wang C, Lewandowska M, Bensaude O, Huang S (2011) Characterization of MRP RNA-protein interactions within the perinucleolar compartment. Mol Biol Cell 22(6):858–867
Koch HG, Moser M, Müller M (2003) Signal recognition particle-dependent protein targeting, universal to all kingdoms of life. Rev Physiol Biochem Pharmacol 146:55–94
Häsler J, Strub K (2006) Alu elements as regulators of gene expression. Nucleic Acids Res 34(19):5491–5497
Fähling M, Steege A, Perlewitz A, Nafz B, Mrowka R, Persson PB, Thiele BJ (2005) Role of nucleolin in posttranscriptional control of MMP-9 expression. Biochim Biophys Acta 1731(1):32–40
Perry RP (1963) Selective effects of actinomycin D on the intracellular distribution of RNA synthesis in tissue culture cells. Exp Cell Res 29:400–406
Higashi K, Matsuhisa T, Kitao A, Sakamoto Y (1968) Selective suppression of nucleolar RNA metabolism in the absence of protein synthesis. Biochim Biophys Acta 166:388–393
Wolin SL, Cedervall T (2002) The La protein. Annu Rev Biochem 71:375–403
White RJ (2004) RNA polymerase III transcription and cancer. Oncogene 23:3208–3216
Lee DY, Clayton DA (1998) Initiation of mitochondrial DNA replication by transcription and R-loop processing. Biol Chem 273:30614–30621
Pruijn GJ, Simons FH, van Venrooij WJ (1997) Intracellular localization and nucleocytoplasmic transport of Ro RNP components. Eur J Cell Biol 74:123–132
Paillard L, Legagneux V, Beverley OH (2003) A functional deadenylation assay identifies human CUG-BP as a deadenylation factor. Biol Cell 95:107–113
Norton JT, Wang C, Gjidoda A, Henry RW, Huang S (2009) Perinucleolar compartment is directly associated with DNA. J Biol Chem 284:4090–4101
Gherzi R, Lee KY, Briata P, Wegmüller D, Moroni C, Karin M, Chen CY (2004) A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol Cell 14:571–583
Norton JT, Pollock CB, Wang C, Schink JC, Kim JJ, Huang S (2008) Perinucleolar compartment prevalence is a phenotypic pan-cancer marker of malignancy. Cancer 113:861–869
Kamath RV, Thor AD, Wang C, Edgerton SM, Slusarczyk A, Leary DJ et al (2005) Perinucleolar compartment prevalence has an independent prognostic value for breast cancer. Cancer Res 65(1):246–253
Kaighn ME, Lechner JF, Narayan KS, Jones LW (1978) Prostate carcinoma: tissue culture cell lines. Natl Cancer Inst Monogr 49:17–21
Kozlowski JM, Fidler IJ, Campbell D, Xu ZL, Kaighn ME, Hart IR (1984) Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res 44:3522–3529
Pettaway CA, Pathak S, Greene G, Ramirez E, Wilson MR, Killion JJ et al (1996) Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res 2:1627–1636
Oh JE, Karlmark KR, Shin JH, Pollak A, Freilinger A, Hengstschlager M et al (2005) Differentiation of neuroblastoma cell line N1E − 115 involves several signaling cascades. Neurochem Res 30(3):333–348
Strickland S, Smith KK, Marotti KR (1980) Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cAMP. Cell 21(2):347–355
Slusarczyk A, Kamath R, Wang C, Anchel D, Pollock C, Lewandowska MA, Fitzpatrick T, Bazett-Jones DP, Huang S (2010) Structure and Function of the Perinucleolar Compartment in Cancer Cells. Cold Spring Harb Symp Quant Biol 75:599–605 Epub 2011
McCutcheon IE, Hentschel SJ, Fuller GN, Jin W, Cote GJ (2004) Expression of the splicing regulator polypyrimidine tract-binding protein in normal and neoplastic brain. Neuro Oncol 6(1):9–14
He X, Pool M, Darcy KM, Lim SB, Auersperg N, Coon JS, Beck WT (2007) Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro. Oncogene 26(34):4961–4968
Storck S, Shukla M, Dimitrov S, Bouvet P (2007) Functions of the histone chaperone nucleolin in diseases. Subcell Biochem 41:125–144
Samant RS, Seraj MJ, Saunders MM, Sakamaki TS, Shevde LA, Harms JF et al (2000) Analysis of mechanisms underlying BRMS1 suppression of metastasis. Clin Exp Metastasis 18(8):683–693
Liu Y, Norton JT, Witshi MA, Xu Q, Lou G, hen Wang C, Appella DH, Chen Z, Huang S (2011) Methoxyethlyamino-numonafide is an efficacious and minimally toxic amonafide derivative in murine models of human cancer. Neoplasia 13(5):453–460
Acknowledgments
We would like to thank the partial funding from the Robert H. Lurie Comprehensive Cancer Center, and grant to SH from NIH, R01 GM078555.
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Norton, J.T., Huang, S. (2013). The Perinucleolar Compartment: RNA Metabolism and Cancer. In: Wu, J. (eds) RNA and Cancer. Cancer Treatment and Research, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-31659-3_6
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DOI: https://doi.org/10.1007/978-3-642-31659-3_6
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