UPF1 at Work: Structural and Mechanistic Insights Into a Master Regulator of Nonsense-Mediated mRNA Decay
Abstract
RNA helicases are central architects of ribonucleoprotein (RNP) organization, coupling nucleoside triphosphate hydrolysis to RNA binding to unwind duplexes, translocate along nucleic acids, displace RNA-binding proteins, and remodel RNP assemblies. Among them, UPF1 (UP-Frameshift 1) is a highly conserved superfamily 1 (SF1) helicase and the pivotal effector of nonsense-mediated mRNA decay (NMD). UPF1 harbors the canonical helicase core motifs required for ATP binding and hydrolysis, RNA interaction, and chemo-mechanical coupling, as well as regulatory domains that fine-tune its catalytic activity and protein-protein interactions. UPF1 displays remarkable enzymatic versatility, acting as an RNA translocase, helicase and RNPase. Its capacity to coordinate these distinct but interconnected activities enables dynamic remodeling of messenger RNPs and positions UPF1 as a multifunctional regulator of RNA fate during NMD. In this review, we integrate current structural and mechanistic insights into UPF1 function and propose a unifying framework that links its biochemical properties to its diverse cellular roles, aiming to reconcile the existing models that describe its mechanism of action.
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BibTeX
@article{mocquet2026upf1,
title = {{UPF1 at Work: Structural and Mechanistic Insights Into a Master Regulator of Nonsense-Mediated mRNA Decay}},
author = {Vincent Mocquet and Francesca Fiorini},
journal = {Journal of Molecular Biology},
year = {2026},
month = jun,
doi = {10.1016/j.jmb.2026.169913},
url = {https://hal.science/hal-05775683v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - UPF1 at Work: Structural and Mechanistic Insights Into a Master Regulator of Nonsense-Mediated mRNA Decay
AU - Vincent Mocquet
AU - Francesca Fiorini
PY - 2026
DA - 2026/06/24
JO - Journal of Molecular Biology
DO - 10.1016/j.jmb.2026.169913
UR - https://hal.science/hal-05775683v1
AB - RNA helicases are central architects of ribonucleoprotein (RNP) organization, coupling nucleoside triphosphate hydrolysis to RNA binding to unwind duplexes, translocate along nucleic acids, displace RNA-binding proteins, and remodel RNP assemblies. Among them, UPF1 (UP-Frameshift 1) is a highly conserved superfamily 1 (SF1) helicase and the pivotal effector of nonsense-mediated mRNA decay (NMD). UPF1 harbors the canonical helicase core motifs required for ATP binding and hydrolysis, RNA interaction, and chemo-mechanical coupling, as well as regulatory domains that fine-tune its catalytic activity and protein-protein interactions. UPF1 displays remarkable enzymatic versatility, acting as an RNA translocase, helicase and RNPase. Its capacity to coordinate these distinct but interconnected activities enables dynamic remodeling of messenger RNPs and positions UPF1 as a multifunctional regulator of RNA fate during NMD. In this review, we integrate current structural and mechanistic insights into UPF1 function and propose a unifying framework that links its biochemical properties to its diverse cellular roles, aiming to reconcile the existing models that describe its mechanism of action.
SN - 0022-2836
SN - 1089-8638
ER -