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U1 snRNA associates with TFIIH and regulates transcriptional initiation

Nature Structural Biology volume 9, pages 800–805 (2002)Cite this article

Abstract

Diverse classes of noncoding RNA, including small nuclear RNAs (snRNAs), play fundamental regulatory roles at many stages of gene expression. For example, recent studies have implicated 7SK RNA and components of the splicing apparatus in the regulation of transcriptional elongation. Here we present the first evidence of the involvement of an snRNA in the regulation of transcriptional initiation. We demonstrate that TFIIH, a general transcription initiation factor, specifically associates with U1 snRNA, a core-splicing component. Analysis of the TFIIH-dependent stages of transcription in a reconstituted system demonstrates that U1 stimulates the rate of formation of the first phosphodiester bond by RNA polymerase II. In addition, a promoter-proximal 5′ splice site recognized by U1 snRNA stimulates TFIIH-dependent reinitiation of productive transcription. Our results suggest that U1 snRNA functions in regulating transcription by RNA Polymerase II in addition to its role in RNA processing.

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Figure 1: Association of TFIIH with RNA.
Figure 2: U1 snRNA specifically associates with TFIIH.
Figure 3: Dissociation of U1 snRNA form TFIIH.
Figure 4: U1 snRNA stimulates TFIIH-dependent abortive initiation by RNA polymerase II.
Figure 5: Reinitiation of transcription is dependent upon U1 snRNA and the proximal 5′ splice site.

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Acknowledgements

We thank A. Catchpole and A. Taylor for help with snRNA cloning, and T. Harder, P. Uguen, P. Cook, O. Bensaude, J. Manley and D. Reinberg for helpful discussions and reagents. A.A. is supported by the Wellcome Trust Career Development Fellowship and by grants from Cancer Research UK and the Edward Abraham Research Fund.

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Authors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Kon Yew Kwek, Shona Murphy, Andre Furger, Benjamin Thomas, William O'Gorman, Nick J. Proudfoot & Alexandre Akoulitchev

  2. Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, 113-8510, Tokyo, Japan

    Hiroshi Kimura

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  1. Kon Yew Kwek
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Correspondence to Alexandre Akoulitchev.

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Kwek, K., Murphy, S., Furger, A. et al. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nat Struct Mol Biol 9, 800–805 (2002). https://doi.org/10.1038/nsb862

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