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
  • 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.