Abstract

Helicases are molecular engines which translocate along nucleic acids (NA) to unwind double-strands or remodel NA–protein complexes. While they have an essential role in genome structure and expression, the rules dictating their processivity remain elusive. Here, we developed single-molecule methods to investigate helicase binding lifetime on DNA. We found that UPF1, a highly processive helicase central to nonsense-mediated mRNA decay (NMD), tightly holds onto NA, allowing long lasting action. Conversely, the structurally similar IGHMBP2 helicase has a short residence time. UPF1 mutants with variable grip on DNA show that grip tightness dictates helicase residence time and processivity. In addition, we discovered via functional studies that a decrease in UPF1 grip impairs NMD efficiency in vivo. Finally, we propose a three-state model with bound, sliding and unbound molecular clips, that can accurately predict the modulation of helicase processivity.

Details

Title
UPF1-like helicase grip on nucleic acids dictates processivity
Author
Kanaan, Joanne 1 ; Raj, Saurabh 2 ; Decourty, Laurence 3 ; Saveanu, Cosmin 3   VIAFID ORCID Logo  ; Croquette, Vincent 4 ; Hervé Le Hir 1 

1  Institut de biologie de l’Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, Paris, France 
2  Institut de biologie de l’Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, Paris, France; Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Université Paris 06, CNRS, Paris, France; Molecular Biophysics Group, Peter Debye Institute for Soft Matter Physics, Universität Leipzig, Leipzig, Germany 
3  Génétique des Interactions Macromoléculaires, Genomes and Genetics Department, Institut Pasteur, Paris, France 
4  Institut de biologie de l’Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, Paris, France; Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Université Paris 06, CNRS, Paris, France 
Pages
1-9
Publication year
2018
Publication date
Sep 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06313-y
ProQuest document ID
2104154218
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.