Abstract
RNA polymerase III (Pol III) makes a variety of small non-coding RNAs, such as tRNA and 5S ribosomal RNA. Increased expression of pol III products is often observed in transformed cells. Much progress has been made in determining how Pol III-dependent transcription is regulated and how it increases in cancers, but the importance of this increase has not been clearly established. New evidence suggests that Pol III output can substantially affect transformation.
Similar content being viewed by others
References
Dieci, G., Fiorino, G., Castelnuovo, M., Teichmann, M. & Pagano, A. The expanding RNA polymerase III transcriptome. Trends Genet. 23, 614–622 (2007).
Thiel, C. T. et al. Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am. J. Hum. Genet. 77, 795–806 (2005).
Nguyen, V. T., Kiss, T., Michels, A. A. & Bensaude, O. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414, 322–325 (2001).
Yang, Z., Zhu, Q., Luo, K. & Zhou, Q. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414, 317–322 (2001).
Mariner, P. D. et al. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol. Cell 29, 499–509 (2008).
Borchert, G. M., Lanier, W. & Davidson, B. L. RNA polymerase III transcribes human microRNAs. Nature Struct. Mol. Biol. 13, 1097–1101 (2006).
Schwartz, L. B., Sklar, V. E. F., Jaehning, S. J., Weinmann, R. & Roeder, R. G. Isolation and partial characterization of the multiple forms of deoxyribonucleic acid-dependent ribonucleic acid polymerase in mouse myeloma MOPC 315. J. Biol. Chem. 249, 5889–5897 (1974).
Winter, A. G. et al. RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumours. Proc. Natl Acad. Sci. USA 97, 12619–12624 (2000).
Chen, W., Bocker, W., Brosius, J. & Tiedge, H. Expression of neural BC200 RNA in human tumours. J. Pathol. 183, 345–351 (1997).
White, R. J. RNA polymerase III transcription and cancer. Oncogene 23, 3208–3216 (2004).
Woiwode, A. et al. PTEN represses RNA polymerase III-dependent transcription by targeting the TFIIIB complex. Mol. Cell. Biol. 28, 4204–4214 (2008).
Chesnokov, I., Chu, W.-M., Botchan, M. R. & Schmid, C. W. p53 inhibits RNA polymerase III-directed transcription in a promoter-dependent manner. Mol. Cell. Biol. 16, 7084–7088 (1996).
Sutcliffe, J. E. et al. RNA polymerase III transcription factor IIIB is a target for repression by pocket proteins p107 and p130. Mol. Cell. Biol. 19, 4255–4261 (1999).
Sutcliffe, J. E., Brown, T. R. P., Allison, S. J., Scott, P. H. & White, R. J. Retinoblastoma protein disrupts interactions required for RNA polymerase III transcription. Mol. Cell. Biol. 20, 9192–9202 (2000).
Crighton, D. et al. p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB. EMBO J. 22, 2810–2820 (2003).
Hirsch, H. A., Jawdekar, G. W., Lee, K.-A., Gu, L. & Henry, R. W. Distinct mechanisms for repression of RNA polymerase III transcription by the retinoblastoma tumor suppressor protein. Mol. Cell. Biol. 24, 5989–5999 (2004).
Scott, P. H. et al. Regulation of RNA polymerase III transcription during cell cycle entry. J. Biol. Chem. 276, 1005–1014 (2001).
Morton, J. P., Kantidakis, T. & White, R. J. RNA polymerase III transcription is repressed in response to the tumour suppressor ARF. Nucleic Acids Res. 35, 3046–3052 (2007).
Willis, I. M. & Moir, R. D. Integration of nutritional and stress signaling pathways by Maf1. Trends Biochem. Sci. 32, 51–53 (2007).
Johnson, S. S., Zhang, C., Fromm, J., Willis, I. M. & Johnson, D. L. Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases. Mol. Cell 26, 367–379 (2007).
Stein, T., Crighton, D., Boyle, J. M., Varley, J. M. & White, R. J. RNA polymerase III transcription can be derepressed by oncogenes or mutations that compromise p53 function in tumours and Li–Fraumeni syndrome. Oncogene 21, 2961–2970 (2002).
Wang, H.-D., Yuh, C.-H., Dang, C. V. & Johnson, D. L. The hepatitis B virus X protein increases the cellular level of TATA-binding protein, which mediates transactivation of RNA polymerase III genes. Mol. Cell. Biol. 15, 6720–6728 (1995).
Felton-Edkins, Z. A. et al. The mitogen-activated protein (MAP) kinase ERK induces tRNA synthesis by phosphorylating TFIIIB. EMBO J. 22, 2422–2432 (2003).
Gomez-Roman, N., Grandori, C., Eisenman, R. N. & White, R. J. Direct activation of RNA polymerase III transcription by c-Myc. Nature 421, 290–294 (2003).
Steiger, D., Furrer, M., Schwinkendorf, D. & Gallant, P. Max-independent functions of Myc in Drosophila melanogaster. Nature Genet. 40, 1084–1091 (2008).
Kenneth, N. S. et al. TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription. Proc. Natl Acad. Sci. USA 104, 14917–14922 (2007).
Johnson, S. A. S., Dubeau, L. & Johnson, D. L. Enhanced RNA polymerase III-dependent transcription is required for oncogenic transformation. J. Biol. Chem. 283, 19184–19191 (2008).
Hoeffler, W. K. & Roeder, R. G. Enhancement of RNA polymerase III transcription by the E1A gene product of adenovirus. Cell 41, 955–963 (1985).
Felton-Edkins, Z. A. & White, R. J. Multiple mechanisms contribute to the activation of RNA polymerase III transcription in cells transformed by papovaviruses. J. Biol. Chem. 277, 48182–48191 (2002).
Felton-Edkins, Z. A. et al. Epstein–Barr virus induces cellular transcription factors to allow active expression of EBER genes by RNA polymerase III. J. Biol. Chem. 281, 33871–33880 (2006).
Johnson, S. A. S. et al. Increased expression of TATA-binding protein, the central transcription factor, can contribute to oncogenesis. Mol. Cell. Biol. 23, 3043–3051 (2003).
Daly, N. L. et al. Deregulation of RNA polymerase III transcription in cervical epithelium in response to high-risk human papillomavirus. Oncogene 24, 880–888 (2005).
Marshall, L., Kenneth, N. S. & White, R. J. Elevated tRNAiMet synthesis can drive cell proliferation and oncogenic transformation. Cell 133, 78–89 (2008).
Kassavetis, G. A. & Geiduschek, E. P. Transcription factor TFIIIB and transcription by RNA polymerase III. Biochem. Soc. Trans. 34, 1082–1087 (2006).
Zetterberg, A. & Killander, D. Quantitative cytophotometric and autoradiographic studies on the rate of protein synthesis during interphase in mouse fibroblasts in vitro. Exp. Cell Res. 40, 1–11 (1965).
Koromilas, A. E., Roy, S., Barber, G. N., Katze, M. G. & Sonenberg, N. Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase. Science 257, 1685–1689 (1992).
Mamane, Y. et al. eIF4E — from translation to transformation. Oncogene 23, 3172–3179 (2004).
Yee, N. S. et al. Mutation of RNA pol III subunit rpc2/polr3b leads to deficiency of subunit Rpc11 and disrupts zebrafish digestive development. PLOS Biol. 5, 2484–2492 (2007).
Mann, C. et al. RPC53 encodes a subunit of Saccharomyces cerevisiae RNA polymerase C (III) whose inactivation leads to a predominantly G1 arrest. Mol. Cell. Biol. 12, 4314–4326 (1992).
Ittmann, M., Ali, J., Greco, A. & Basilico, C. The gene complementing a temperature-sensitive cell cycle mutant of BHK cells is the human homologue of the yeast RPC53 gene, which encodes a subunit of RNA polymerase C (III). Cell Growth Diff. 4, 503–511 (1993).
White, R. J. RNA polymerase III transcription — a battleground for tumour suppressors and oncogenes. Eur J. Cancer 40, 21–27 (2004).
Tang, R.-B. et al. Increased level of Polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue. Mol. Carcinogen. 42, 93–96 (2005).
Kohnoe, S., Maehara, Y. & Endo, H. A systemtatic survey of repetitive sequences abundantly expressed in rat tumors. Biochim. Biophys. Acta 909, 107–114 (1987).
White, R. J., Stott, D. & Rigby, P. W. J. Regulation of RNA polymerase III transcription in response to F9 embryonal carcinoma stem cell differentiation. Cell 59, 1081–1092 (1989).
Chen, W., Heierhorst, J., Brosius, J. & Tiedge, H. Expression of neural BC1 RNA: induction in murine tumours. Eur. J. Cancer 33, 288–292 (1997).
Arrand, J. R. & Rymo, L. Characterization of the major Epstein–Barr virus-specific RNA in Burkitt lymphoma-derived cells. J. Virol. 41, 376–389 (1982).
Tugwood, J. D. et al. EBV-specific transcription in normal and malignant nasopharyngeal biopsies and in lymphocytes from healthy donors and infectious mononucleosis patients. J. Gen. Virol. 68, 1081–1091 (1987).
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Related links
Related links
DATABASES
National Cancer Institute Drug Dictionary
OMIM
FURTHER INFORMATION
SUPPLEMENTARY INFORMATION
See online article
Rights and permissions
About this article
Cite this article
Marshall, L., White, R. Non-coding RNA production by RNA polymerase III is implicated in cancer. Nat Rev Cancer 8, 911–914 (2008). https://doi.org/10.1038/nrc2539
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrc2539
- Springer Nature Limited
This article is cited by
-
Reconstructing disease dynamics for mechanistic insights and clinical benefit
Nature Communications (2023)
-
Biosynthesis of brain cytoplasmic 200 RNA
Scientific Reports (2017)
-
Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer
Scientific Reports (2016)
-
Allele-specific loss and transcription of the miR-15a/16-1 cluster in chronic lymphocytic leukemia
Leukemia (2015)
-
INMAP, a novel truncated version of POLR3B, represses AP-1 and p53 transcriptional activity
Molecular and Cellular Biochemistry (2013)