Structural and Functional Insights into the Human Upf1 Helicase Core

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 Dec 13

PMID 17159905

Citations 91

Authors

Zhihong Cheng

Denise Muhlrad

Meng Kiat Lim

Roy Parker

Haiwei Song

Affiliations

Soon will be listed here.

Abstract

Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance pathway that recognizes and degrades aberrant mRNAs containing premature stop codons. A critical protein in NMD is Upf1p, which belongs to the helicase super family 1 (SF1), and is thought to utilize the energy of ATP hydrolysis to promote transitions in the structure of RNA or RNA-protein complexes. The crystal structure of the catalytic core of human Upf1p determined in three states (phosphate-, AMPPNP- and ADP-bound forms) reveals an overall structure containing two RecA-like domains with two additional domains protruding from the N-terminal RecA-like domain. Structural comparison combined with mutational analysis identifies a likely single-stranded RNA (ssRNA)-binding channel, and a cycle of conformational change coupled to ATP binding and hydrolysis. These conformational changes alter the likely ssRNA-binding channel in a manner that can explain how ATP binding destabilizes ssRNA binding to Upf1p.

Citing Articles

RNA anchoring of Upf1 facilitates recruitment of Dcp2 in the NMD decapping complex.

Ruiz-Gutierrez N, Dupas J, Auquier E, Barbarin-Bocahu I, Gaudon-Plesse C, Saveanu C Nucleic Acids Res. 2025; 53(5).

PMID: 40071934 PMC: 11897886. DOI: 10.1093/nar/gkaf160.

Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans.

Barbarin-Bocahu I, Ulryck N, Rigobert A, Ruiz Gutierrez N, Decourty L, Raji M PLoS Biol. 2024; 22(9):e3002821.

PMID: 39331656 PMC: 11463774. DOI: 10.1371/journal.pbio.3002821.

CoCoNuTs are a diverse subclass of Type IV restriction systems predicted to target RNA.

Bell R, Sahakyan H, Makarova K, Wolf Y, Koonin E Elife. 2024; 13.

PMID: 38739430 PMC: 11090510. DOI: 10.7554/eLife.94800.

UPF1 ATPase autoinhibition and activation modulate RNA binding kinetics and NMD efficiency.

Chapman J, Youle A, Grimme A, Neuman K, Hogg J Nucleic Acids Res. 2024; 52(9):5376-5391.

PMID: 38412299 PMC: 11109973. DOI: 10.1093/nar/gkae136.

Messenger RNA Surveillance: Current Understanding, Regulatory Mechanisms, and Future Implications.

Das R, Panigrahi G Mol Biotechnol. 2024; 67(2):393-409.

PMID: 38411790 DOI: 10.1007/s12033-024-01062-4.

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