Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family
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Bronislava Leonaitė [1] ; Zhong Han [3] ; Jérôme Basquin [1] ; Fabien Bonneau [1] ; Domenico Libri [2] ; Odil Porrua [2] ; Elena Conti [1]
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[1] Max Planck Institute of Biochemistry
Max Planck Institute of Biochemistry
Kreisfreie Stadt München, Alemania
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[2] Université Denis Diderot
Université Denis Diderot
París, Francia
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[3] 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
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- Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 11, 2017, págs. 1590-1604
- Idioma: inglés
- Enlaces
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Resumen
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.
