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Non-coding-RNA regulators of RNA polymerase II transcription

Nature Reviews Molecular Cell Biology volume 7, pages 612–616 (2006)Cite this article

Abstract

Several non-coding RNAs (ncRNAs) that regulate eukaryotic mRNA transcription have recently been discovered. Their mechanisms of action and biological roles are extremely diverse, which indicates that, so far, we have only had a glimpse of this new class of regulatory factor. Many surprises are likely to be revealed as further ncRNA transcriptional regulators are identified and characterized.

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Figure 1: The structure of a non-coding RNA is crucial for its function.
Figure 2: Eukaryotic RNA polymerase II transcription is a complex process that can be regulated at many points.

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References

  1. Storz, G., Altuvia, S. & Wassarman, K. M. An abundance of RNA regulators. Annu. Rev. Biochem. 74, 199–217 (2005).

    Article  CAS  Google Scholar 

  2. Narlikar, G. J., Fan, H. Y. & Kingston, R. E. Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475–487 (2002).

    Article  CAS  Google Scholar 

  3. Kadonaga, J. T. Regulation of RNA polymerase II transcription by sequence-specific DNA binding factors. Cell 116, 247–257 (2004).

    Article  CAS  Google Scholar 

  4. Smale, S. T. & Kadonaga, J. T. The RNA polymerase II core promoter. Annu. Rev. Biochem. 72, 449–479 (2003).

    Article  CAS  Google Scholar 

  5. Naar, A. M., Lemon, B. D. & Tjian, R. Transcriptional coactivator complexes. Annu. Rev. Biochem. 70, 475–501 (2001).

    Article  CAS  Google Scholar 

  6. Lanz, R. B. et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97, 17–27 (1999).

    Article  CAS  Google Scholar 

  7. Lanz, R. B., Razani, B., Goldberg, A. D. & O'Malley, B. W. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proc. Natl Acad. Sci. USA 99, 16081–16086 (2002).

    Article  CAS  Google Scholar 

  8. Kuwabara, T., Hsieh, J., Nakashima, K., Taira, K. & Gage, F. H. A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 116, 779–793 (2004).

    Article  CAS  Google Scholar 

  9. Shamovsky, I., Ivannikov, M., Kandel, E. S., Gershon, D. & Nudler, E. RNA-mediated response to heat shock in mammalian cells. Nature 440, 556–560 (2006).

    Article  CAS  Google Scholar 

  10. Willingham, A. T. et al. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309, 1570–1573 (2005).

    Article  CAS  Google Scholar 

  11. Orphanides, G., Lagrange, T. & Reinberg, D. The general transcription factors of RNA polymerase II. Genes Dev. 10, 2657–2683 (1996).

    Article  CAS  Google Scholar 

  12. Reines, D., Conaway, J. W. & Conaway, R. C. The RNA polymerase II general elongation factors. Trends Biochem. Sci. 21, 351–355 (1996).

    Article  CAS  Google Scholar 

  13. Kwek, K. Y. et al. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nature Struct. Biol. 9, 800–805 (2002).

    CAS  PubMed  Google Scholar 

  14. O'Gorman, W., Thomas, B., Kwek, K. Y., Furger, A. & Akoulitchev, A. Analysis of U1 small nuclear RNA interaction with cyclin H. J. Biol. Chem. 280, 36920–36925 (2005).

    Article  CAS  Google Scholar 

  15. 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).

    Article  CAS  Google Scholar 

  16. 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).

    Article  CAS  Google Scholar 

  17. Yik, J. H. et al. Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol. Cell 12, 971–982 (2003).

    Article  CAS  Google Scholar 

  18. Allen, T. A., Von Kaenel, S., Goodrich, J. A. & Kugel, J. F. The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock. Nature Struct. Mol. Biol. 11, 816–821 (2004).

    Article  CAS  Google Scholar 

  19. Espinoza, C. A., Allen, T. A., Hieb, A. R., Kugel, J. F. & Goodrich, J. A. B2 RNA binds directly to RNA polymerase II to repress transcript synthesis. Nature Struct. Mol. Biol. 11, 822–829 (2004).

    Article  CAS  Google Scholar 

  20. Liu, W. M., Chu, W. M., Choudary, P. V. & Schmid, C. W. Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. Nucl. Acids Res. 23, 1758–1765 (1995).

    Article  CAS  Google Scholar 

  21. Wassarman, K. M. & Storz, G. 6S RNA regulates E. coli RNA polymerase activity. Cell 101, 613–623 (2000).

    Article  CAS  Google Scholar 

  22. Thomas, M. et al. Selective targeting and inhibition of yeast RNA polymerase II by RNA aptamers. J. Biol. Chem. 272, 27980–27986 (1997).

    Article  CAS  Google Scholar 

  23. Kettenberger, H. et al. Structure of an RNA polymerase II–RNA inhibitor complex elucidates transcription regulation by noncoding RNAs. Nature Struct. Mol. Biol. 13, 44–48 (2006).

    Article  CAS  Google Scholar 

  24. Kugel, J. F. & Goodrich, J. A. Translocation after synthesis of a four-nucleotide RNA commits RNA polymerase II to promoter escape. Mol. Cell. Biol. 22, 762–773 (2002).

    Article  CAS  Google Scholar 

  25. Boumil, R. M. & Lee, J. T. Forty years of decoding the silence in X-chromosome inactivation. Hum. Mol. Genet. 10, 2225–2232 (2001).

    Article  CAS  Google Scholar 

  26. Almeida, R. & Allshire, R. C. RNA silencing and genome regulation. Trends Cell Biol. 15, 251–258 (2005).

    Article  CAS  Google Scholar 

  27. Gollnick, P. & Babitzke, P. Transcription attenuation. Biochim. Biophys. Acta 1577, 240–250 (2002).

    Article  CAS  Google Scholar 

  28. Rosen, C. A., Sodroski, J. G. & Haseltine, W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell 41, 813–823 (1985).

    Article  CAS  Google Scholar 

  29. Selby, M. J., Bain, E. S., Luciw, P. A. & Peterlin, B. M. Structure, sequence, and position of the stem–loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 3, 547–558 (1989).

    Article  CAS  Google Scholar 

  30. Feng, S. & Holland, E. C. HIV-1 tat trans-activation requires the loop sequence within tar. Nature 334, 165–167 (1988).

    Article  CAS  Google Scholar 

  31. Roy, S., Delling, U., Chen, C. H., Rosen, C. A. & Sonenberg, N. A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. Genes Dev. 4, 1365–1373 (1990).

    Article  CAS  Google Scholar 

  32. Teixeira, A. et al. Autocatalytic RNA cleavage in the human β-globin pre-mRNA promotes transcription termination. Nature 432, 526–530 (2004).

    Article  CAS  Google Scholar 

  33. Kaneko, S. & Manley, J. L. The mammalian RNA polymerase II C-terminal domain interacts with RNA to suppress transcription-coupled 3′ end formation. Mol. Cell 20, 91–103 (2005).

    Article  CAS  Google Scholar 

  34. Tian, Y. et al. Dissecting protein:protein interactions between transcription factors with an RNA aptamer. RNA 1, 317–326 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhai, G., Iskandar, M., Barilla, K. & Romaniuk, P. J. Characterization of RNA aptamer binding by the Wilms' tumor suppressor protein WT1. Biochemistry 40, 2032–2040 (2001).

    Article  CAS  Google Scholar 

  36. Park, M. W., Choi, K. H. & Jeong, S. Inhibition of the DNA binding by the TCF-1 binding RNA aptamer. Biochem. Biophys. Res. Commun. 330, 11–17 (2005).

    Article  CAS  Google Scholar 

  37. Ghosh, G., Huang, D. B. & Huxford, T. Molecular mimicry of the NF-κB DNA target site by a selected RNA aptamer. Curr. Opin. Struct. Biol. 14, 21–27 (2004).

    Article  CAS  Google Scholar 

  38. Fan, X., Shi, H., Adelman, K. & Lis, J. T. Probing TBP interactions in transcription initiation and reinitiation with RNA aptamers that act in distinct modes. Proc. Natl Acad. Sci. USA 101, 6934–6939 (2004).

    Article  CAS  Google Scholar 

  39. Fan, X., Shi, H. & Lis, J. T. Distinct transcriptional responses of RNA polymerases I, II and III to aptamers that bind TBP. Nucl. Acids Res. 33, 838–845 (2005).

    Article  CAS  Google Scholar 

  40. Saha, S., Ansari, A. Z., Jarrell, K. A. & Ptashne, M. RNA sequences that work as transcriptional activating regions. Nucl. Acids Res. 31, 1565–1570 (2003).

    Article  CAS  Google Scholar 

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Acknowledgements

Research in the authors' laboratory is supported by the National Institutes of Health and the National Science Foundation.

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Authors and Affiliations

  1. the Department of Chemistry and Biochemistry, University of Colorado at Boulder, 215 UCB, Boulder, 80309-0215, Colorado, USA

    James A. Goodrich & Jennifer F. Kugel

  2. James A. Goodrich & Jennifer F. Kugel

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  1. James A. Goodrich
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  2. Jennifer F. Kugel
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The authors declare no competing financial interests.

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Goodrich, J., Kugel, J. Non-coding-RNA regulators of RNA polymerase II transcription. Nat Rev Mol Cell Biol 7, 612–616 (2006). https://doi.org/10.1038/nrm1946

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