2. Academic Validation
  3. UPF1-like helicase grip on nucleic acids dictates processivity

UPF1-like helicase grip on nucleic acids dictates processivity

  • Nat Commun. 2018 Sep 14;9(1):3752. doi: 10.1038/s41467-018-06313-y.
Joanne Kanaan 1,  Saurabh Raj 1 2 3,  Laurence Decourty 4,  Cosmin Saveanu 4,  Vincent Croquette 5 6,  Hervé Le Hir 7
Affiliations

Affiliations

  • 1 Institut de biologie de l'Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, 46 rue d'Ulm, 75005, Paris, France.
  • 2 Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Université Paris 06, CNRS, 24 rue Lhomond, 75005, Paris, France.
  • 3 Molecular Biophysics Group, Peter Debye Institute for Soft Matter Physics, Universität Leipzig, Linnéstraße 5, 04103, Leipzig, Germany.
  • 4 Génétique des Interactions Macromoléculaires, Genomes and Genetics Department, Institut Pasteur, 25-28 rue du docteur Roux, 75015, Paris, France.
  • 5 Institut de biologie de l'Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, 46 rue d'Ulm, 75005, Paris, France. [email protected].
  • 6 Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Université Paris 06, CNRS, 24 rue Lhomond, 75005, Paris, France. [email protected].
  • 7 Institut de biologie de l'Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, 46 rue d'Ulm, 75005, Paris, France. [email protected].
PMID: 30218034 DOI: 10.1038/s41467-018-06313-y
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.

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