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EMBO J. 2017 Jun 1;36(11):1590-1604. doi: 10.15252/embj.201696174. Epub 2017 Apr 13.

Sen1 has unique structural features grafted on the architecture of the Upf1-like helicase family.

Author information

1
Max Planck Institute of Biochemistry, Munich, Germany.
2
Graduate School of Quantitative Biosciences, Ludwig-Maximilians-University, Munich, Germany.
3
Institut Jacques Monod, Centre Nationale pour la Recherche Scientifique (CNRS), UMR 7592 Université Paris Diderot, Paris, France.
4
Université Paris-Saclay, Gif sur Yvette, France.
5
Institut Jacques Monod, Centre Nationale pour la Recherche Scientifique (CNRS), UMR 7592 Université Paris Diderot, Paris, France odil.porrua@ijm.fr conti@biochem.mpg.de.
6
Max Planck Institute of Biochemistry, Munich, Germany odil.porrua@ijm.fr conti@biochem.mpg.de.

Abstract

The superfamily 1B (SF1B) helicase Sen1 is an essential protein that plays a key role in the termination of non-coding transcription in yeast. Here, we identified the ~90 kDa helicase core of Saccharomyces cerevisiae Sen1 as sufficient for transcription termination in vitro and determined the corresponding structure at 1.8 Å resolution. In addition to the catalytic and auxiliary subdomains characteristic of the SF1B family, Sen1 has a distinct and evolutionarily conserved structural feature that "braces" the helicase core. Comparative structural analyses indicate that the "brace" is essential in shaping a favorable conformation for RNA binding and unwinding. We also show that subdomain 1C (the "prong") is an essential element for 5'-3' unwinding and for Sen1-mediated transcription termination in vitro Finally, yeast Sen1 mutant proteins mimicking the disease forms of the human orthologue, senataxin, show lower capacity of RNA unwinding and impairment of transcription termination in vitro The combined biochemical and structural data thus provide a molecular model for the specificity of Sen1 in transcription termination and more generally for the unwinding mechanism of 5'-3' helicases.

KEYWORDS:

RNA helicases; non‐coding transcription; transcription termination

PMID:
28408439
PMCID:
PMC5452015
DOI:
10.15252/embj.201696174
[Indexed for MEDLINE]
Free PMC Article

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