Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - SMG7 acts as a molecular link between mRNA surveillance and mRNA decay
AU - Unterholzner, Leonie
AU - Izaurralde, Elisa
PY - 2004/11/19
Y1 - 2004/11/19
N2 - 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.
AB - 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.
KW - Blotting, Western
KW - Carbocyanines
KW - Carrier Proteins
KW - Cytoplasm
KW - Dactinomycin
KW - Frameshift Mutation
KW - Genes, Reporter
KW - HeLa Cells
KW - Humans
KW - Luciferases
KW - Microscopy, Fluorescence
KW - Mutation
KW - Nucleic Acid Synthesis Inhibitors
KW - Plasmids
KW - Protein Structure, Tertiary
KW - RNA Interference
KW - RNA, Messenger
KW - RNA, Small Interfering
KW - Recombinant Fusion Proteins
KW - Ribonucleoproteins, Small Nuclear
KW - Templates, Genetic
KW - Time Factors
KW - Trans-Activators
KW - Transfection
U2 - 10.1016/j.molcel.2004.10.013
DO - 10.1016/j.molcel.2004.10.013
M3 - Journal article
C2 - 15546618
VL - 16
SP - 587
EP - 596
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 4
ER -