A Highly Conserved Region Essential for NMD in the Upf2 N-terminal Domain

Overview

Journal J Mol Biol

Publisher Elsevier

Specialties Microbiology
Molecular Biology

Date 2014 Oct 4

PMID 25277656

Citations 12

Authors

Zaineb Fourati

Bijoyita Roy

Claudia Millan

Pierre-Damien Coureux

Stephanie Kervestin

Herman Van Tilbeurgh

Feng He

Isabel Uson

Allan Jacobson

Marc Graille

Affiliations

Soon will be listed here.

Abstract

Upf1, Upf2, and Upf3 are the principal regulators of nonsense-mediated mRNA decay (NMD), a cytoplasmic surveillance pathway that accelerates the degradation of mRNAs undergoing premature translation termination. These three proteins interact with each other, the ribosome, the translation termination machinery, and multiple mRNA decay factors, but the precise mechanism allowing the selective detection and degradation of nonsense-containing transcripts remains elusive. Here, we have determined the crystal structure of the N-terminal mIF4G domain from Saccharomyces cerevisiae Upf2 and identified a highly conserved region in this domain that is essential for NMD and independent of Upf2's binding sites for Upf1 and Upf3. Mutations within this conserved region not only inactivate NMD but also disrupt Upf2 binding to specific proteins, including Dbp6, a DEAD-box helicase. Although current models indicate that Upf2 functions principally as an activator of Upf1 and a bridge between Upf1 and Upf3, our data suggest that it may also serve as a platform for the association of additional factors that play roles in premature translation termination and NMD.

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.

UPF1 regulates mRNA stability by sensing poorly translated coding sequences.

Musaev D, Abdelmessih M, Vejnar C, Yartseva V, Weiss L, Strayer E Cell Rep. 2024; 43(4):114074.

PMID: 38625794 PMC: 11259039. DOI: 10.1016/j.celrep.2024.114074.

Characterization of the mIF4G Domains in the RNA Surveillance Protein Upf2p.

Colon E, Haddock 3rd L, Lasalde C, Lin Q, Ramirez-Lugo J, Gonzalez C Curr Issues Mol Biol. 2024; 46(1):244-261.

PMID: 38248319 PMC: 10814901. DOI: 10.3390/cimb46010017.

Sensing of H2O2-induced oxidative stress by the UPF factor complex is crucial for activation of catalase-3 expression in Neurospora.

Shen S, Zhang C, Meng Y, Cui G, Wang Y, Liu X PLoS Genet. 2023; 19(10):e1010985.

PMID: 37844074 PMC: 10578600. DOI: 10.1371/journal.pgen.1010985.

Eukaryotic mRNA decapping factors: molecular mechanisms and activity.

He F, Jacobson A FEBS J. 2022; 290(21):5057-5085.

PMID: 36098474 PMC: 10008757. DOI: 10.1111/febs.16626.

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