DOI: 10.1073/pnas.0903188106. 7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development

7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development

10.1073/pnas.0903188106

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Eukaryotic gene expression is commonly controlled at the level of RNA polymerase II (RNAPII) pausing subsequent to transcription initiation. Transcription elongation is stimulated by the positive transcription elongation factor b (P-TEFb) kinase, which is suppressed within the 7SK small nuclear ribonucleoprotein (7SK snRNP). However, the biogenesis and functional significance of 7SK snRNP remain poorly understood. Here, we report that LARP7, BCDIN3, and the noncoding 7SK small nuclear RNA (7SK) are vital for the formation and stability of a cell stress-resistant core 7SK snRNP. Our functional studies demonstrate that 7SK snRNP is not only critical for controlling transcription elongation, but also for regulating alternative splicing of pre-mRNAs. Using a transient expression splicing assay, we find that 7SK snRNP disintegration promotes inclusion of an alternative exon via the increased occupancy of P-TEFb, Ser2-phosphorylated (Ser2-P) RNAPII, and the splicing factor SF2/ASF at the minigene. Importantly, knockdown of larp7 or bcdin3 orthologues in zebrafish embryos destabilizes 7SK and causes severe developmental defects and aberrant splicing of analyzed transcripts. These findings reveal a key role for P-TEFb in coupling transcription elongation with alternative splicing, and suggest that maintaining core 7SK snRNP is essential for vertebrate development.

Bibliography

Barboric, M., Lenasi, T., Chen, H., Johansen, E. B., Guo, S., & Peterlin, B. M. (2009). 7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development. Proceedings of the National Academy of Sciences, 106(19), 7798â7803.

Authors 6

Matjaz Barboric (first)
Tina Lenasi (additional)
Hui Chen (additional)
Eric B. Johansen (additional)
Su Guo (additional)
B. Matija Peterlin (additional)

References 34 Referenced 137

Dates

Type	When
Created	16 years, 3 months ago (April 27, 2009, 9:50 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:17 p.m.)
Indexed	1 month, 1 week ago (July 14, 2025, 11:27 p.m.)
Issued	16 years, 3 months ago (May 12, 2009)
Published	16 years, 3 months ago (May 12, 2009)
Published Online	16 years, 3 months ago (May 12, 2009)
Published Print	16 years, 3 months ago (May 12, 2009)

Funders 0

None

BibTeX

@article{Barboric_2009, title={7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development}, volume={106}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0903188106}, DOI={10.1073/pnas.0903188106}, number={19}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Barboric, Matjaz and Lenasi, Tina and Chen, Hui and Johansen, Eric B. and Guo, Su and Peterlin, B. Matija}, year={2009}, month=may, pages={7798–7803} }

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