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Joanne Kanaan

Doctorante financée par le LabEx MemoLife

UPF1-like helicase grip on nucleic acids dictates processivity.

Joanne Kanaan, Saurabh Raj, Laurence Decourty, Cosmin Saveanu, Vincent Croquette & Hervé Le Hir.


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.

More information

Nat Commun. 2018 Sep 14 ;9(1):3752. doi : 10.1038/s41467-018-06313-y.