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Stimulatory effect of splicing factors on transcriptional elongation

Nature volume 414, pages 929–933 (2001)Cite this article

Abstract

Transcription and pre-mRNA splicing are tightly coupled gene expression events in eukaryotic cells1,2. An interaction between the carboxy-terminal domain of the largest subunit of RNA polymerase (Pol) II and components of the splicing machinery is postulated to mediate this coupling3,4,5. Here, we show that splicing factors function directly to promote transcriptional elongation, demonstrating that transcription is more intimately coupled to splicing than previously thought. The spliceosomal U small nuclear ribonucleoproteins (snRNPs) interact with human transcription elongation factor TAT-SF1 (refs 6,7,8,9) and strongly stimulate polymerase elongation when directed to an intron-free human immunodeficiency virus-1 (HIV-1) template. This effect is likely to be mediated through the binding of TAT-SF1 to elongation factor P-TEFb10, a proposed component of the transcription elongation complex11,12. Inclusion of splicing signals in the nascent transcript further stimulates transcription, supporting the notion that the recruitment of U snRNPs near the elongating polymerase is important for transcription. Because the TAT-SF1–U snRNP complex also stimulates splicing in vitro, it may serve as a dual-function factor to couple transcription and splicing and to facilitate their reciprocal activation.

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Figure 1: The CYCT1 C-terminal domain interacts with a TAT-SF1-associated transcription elongation activity.
Figure 2: Both the N-terminal RRMs and the C-terminal acidic domain of TAT-SF1 are required for transactivation.
Figure 3: The TAT-SF1-associated U snRNPs are active in both transcription and splicing.
Figure 4: Splicing signals in nascent transcripts stimulate transcription.

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Acknowledgements

We thank B. Blencowe for the gift of antisense RNA oligonucleotide and advice on the depletion procedures; E. Labourier, D. Rio, J. Underwood, D. Black and H. Wu for reagents; E. Logue and L. Zhou for technical assistance; and K. Luo, I. von Reis and S. Stroschein for discussions. Supported by grants from the National Institutes of Health to Q.Z. and the University of California Universitywide AIDS Research Program to Y.W.F.

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  1. Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, 94720-3206, California, USA

    Yick W. Fong & Qiang Zhou

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  1. Yick W. Fong
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  2. Qiang Zhou
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Correspondence to Qiang Zhou.

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Fong, Y., Zhou, Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature 414, 929–933 (2001). https://doi.org/10.1038/414929a

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