SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway - PubMed (original) (raw)

SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway

Noemi Fukuhara et al. Mol Cell. 2005.

Free article

Abstract

In metazoa, regulation of the phosphorylation state of UPF1 is crucial for nonsense-mediated mRNA decay (NMD), a process by which aberrant mRNAs containing nonsense mutations are degraded. UPF1 is targeted for dephosphorylation by three related proteins, SMG5, SMG6, and SMG7. We report here the crystal structure of the N-terminal domain of SMG7. The structure reveals that SMG7 contains a 14-3-3-like domain. Residues that bind phosphoserine-containing peptides in 14-3-3 are conserved at the equivalent positions in SMG7. Mutation of these residues impairs UPF1 binding to SMG7 in vitro and UPF1 recruitment to cytoplasmic mRNA decay foci in vivo, suggesting that SMG7 acts as an adaptor in targeting mRNAs associated with phosphorylated UPF1 for degradation. The 14-3-3 site of SMG7 is conserved in SMG5 and SMG6. These data also imply that the homologous human Est1 might have a 14-3-3 function at telomeres, and that phosphorylation events may be important for telomerase regulation.

PubMed Disclaimer

Cited by

eIF4E-bound mRNPs are substrates for nonsense-mediated mRNA decay in mammalian cells.
Rufener SC, Mühlemann O. Rufener SC, et al. Nat Struct Mol Biol. 2013 Jun;20(6):710-7. doi: 10.1038/nsmb.2576. Epub 2013 May 12. Nat Struct Mol Biol. 2013. PMID: 23665581
Yeast hEST1A/B (SMG5/6)-like proteins contribute to environment-sensing adaptive gene expression responses.
Lai X, Beilharz T, Au WC, Hammet A, Preiss T, Basrai MA, Heierhorst J. Lai X, et al. G3 (Bethesda). 2013 Oct 3;3(10):1649-59. doi: 10.1534/g3.113.006924. G3 (Bethesda). 2013. PMID: 23893744 Free PMC article.
Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay.
Durand S, Franks TM, Lykke-Andersen J. Durand S, et al. Nat Commun. 2016 Aug 11;7:12434. doi: 10.1038/ncomms12434. Nat Commun. 2016. PMID: 27511142 Free PMC article.
Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2.
Clerici M, Deniaud A, Boehm V, Gehring NH, Schaffitzel C, Cusack S. Clerici M, et al. Nucleic Acids Res. 2014 Feb;42(4):2673-86. doi: 10.1093/nar/gkt1197. Epub 2013 Nov 23. Nucleic Acids Res. 2014. PMID: 24271394 Free PMC article.
Identification of SMG6 cleavage sites and a preferred RNA cleavage motif by global analysis of endogenous NMD targets in human cells.
Schmidt SA, Foley PL, Jeong DH, Rymarquis LA, Doyle F, Tenenbaum SA, Belasco JG, Green PJ. Schmidt SA, et al. Nucleic Acids Res. 2015 Jan;43(1):309-23. doi: 10.1093/nar/gku1258. Epub 2014 Nov 27. Nucleic Acids Res. 2015. PMID: 25429978 Free PMC article.

SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway - PubMed (original) (raw)