SMG7 acts as a molecular link between mRNA surveillance and mRNA decay.
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that eliminates mRNAs containing premature termination codons (PTCs). The proteins UPF1, SMG5, SMG6, and SMG7 are essential NMD factors in metazoa. SMG5 and SMG7 form a complex with UPF1 and interact with each other via their N-terminal domains. Here we show that SMG5 and SMG7 colocalize in cytoplasmic mRNA decay bodies, while SMG6 forms separate cytoplasmic foci. When SMG7 is tethered to a reporter transcript, it elicits its degradation, bypassing the requirement for a PTC, UPF1, SMG5, or SMG6. This activity is mediated by the C-terminal domain of SMG7. In contrast, SMG5 requires SMG7 to trigger mRNA decay and to localize to decay bodies. Our findings indicate that SMG7 provides a link between the NMD and the mRNA degradation machinery by interacting with SMG5 and UPF1 via its N-terminal domain and targeting bound transcripts for decay via its C-terminal domain.
Unterholzner
Leonie
L
European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Izaurralde
Elisa
E
D015153:Blotting, Western; D002232:Carbocyanines; D002352:Carrier Proteins / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D016368:Frameshift Mutation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010957:Plasmids; D017434:Protein Structure, Tertiary; D020365:RNA Helicases; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D013698:Templates, Genetic; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection
D002232:Carbocyanines; D002352:Carrier Proteins; C485751:LSM4 protein, human; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D017411:Ribonucleoproteins, Small Nuclear; C494578:SMG7 protein, human; D015534:Trans-Activators; C089187:cyanine dye 3; D003609:Dactinomycin; D008156:Luciferases; D020365:RNA Helicases; C101828:UPF1 protein, human