UPF1-like helicase grip on nucleic acids dictates processivity.

Publication Type:

Journal Article

Source:

Nature communications, Volume 9, Issue 1, p.3752 (2018)

DOI:

10.1038/s41467-018-06313-y

Keywords:

DNA; DNA-Binding Proteins; Humans; Nonsense Mediated mRNA Decay; Nucleic Acids; RNA Helicases; Saccharomyces cerevisiae Proteins; Time Factors; Trans-Activators; Transcription Factors

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.