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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 1 - Protein Evolution (A. Lupas)     Display Documents



ID: 561542.0, MPI für Entwicklungsbiologie / Abteilung 1 - Protein Evolution (A. Lupas)
SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay
Authors:Kashima, I.; Jonas, S.; Jayachandran, U.; Buchwald, G.; Conti, E.; Lupas, A. N.; Izaurralde, E.
Date of Publication (YYYY-MM-DD):2010-11-01
Title of Journal:Genes & Development
Volume:24
Issue / Number:21
Start Page:2440
End Page:2450
Audience:Not Specified
Abstract / Description:Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades mRNAs containing premature stop codons (PTCs). In vertebrates, PTCs trigger efficient NMD when located upstream of an exon junction complex (EJC). Degradation of PTC-containing mRNAs requires the endonucleolytic activity of SMG6, a conserved NMD factor; nevertheless, the precise role for the EJC in NMD and how the SMG6 endonuclease is recruited to NMD targets have been unclear. Here we show that SMG6 interacts directly with the EJC via two conserved EJC-binding motifs (EBMs). We further show that the SMG6-EJC interaction is required for NMD. Our results reveal an unprecedented role for the EJC in recruiting the SMG6 endonuclease to NMD targets. More generally, our findings identify the EBM as a protein motif present in a handful of proteins, and suggest that EJCs establish multiple and mutually exclusive interactions with various protein partners, providing a plausible explanation for the myriad functions performed by this complex in post-transcriptional mRNA regulation.
Free Keywords:Amino Acid Motifs/*genetics; Amino Acid Sequence; Binding Sites/genetics; Blotting, Western; Codon, Nonsense; Exons/*genetics; Green Fluorescent Proteins/genetics/metabolism; HEK293 Cells; Hela Cells; Humans; Immunoprecipitation; Molecular Sequence Data; Protein Binding; RNA Interference; RNA Stability/*genetics; RNA, Messenger/genetics/metabolism; RNA-Binding Proteins/genetics/metabolism; Sequence Homology, Amino Acid; Telomerase/genetics/*metabolism
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilung 1 - Proteinevolution (Andrei Lupas)/
External Affiliations:%G eng
Identifiers:ISSN:1549-5477 (Electronic) 0890-9369 (Linking) %R gad.604610 [pii] 10.1101/gad.604610
URL:http://www.ncbi.nlm.nih.gov/pubmed/20930030
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