TY - JOUR
T1 - Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA
AU - Matsuda, Daiki
AU - Hosoda, Nao
AU - Kim, Yoon Ki
AU - Maquat, Lynne E.
N1 - Funding Information:
We thank F. Lejeune and X. Li for contributions to early phases of this work, O. Isken for comments on the manuscript, E. Izaurralde (Max Planck Institute-Tübingen) for anti-CBP80, H. Baumann and B. Held (Roswell Park Cancer Institute) for anti-MUP, G. Dreyfuss (University of Pennsylvania) for anti-Y14, A. Mayeda (Fujita Health University) for anti-RNPS1, N. Sonenberg (McGill University) for anti-eIF3b, anti-eIF4AIII, anti-4E-BP1 and the pACTAG2 plasmids, and D. Scofield for helpful conversations. This work was supported by
PY - 2007/10
Y1 - 2007/10
N2 - Nonsense-mediated mRNA decay (NMD) generally eliminates messenger RNAs that prematurely terminate translation and occurs in all eukaryotes that have been studied, although with mechanistic variations. In mammals, NMD seems to be restricted to newly synthesized mRNA that is bound by the cap-binding heterodimer CBP80-CBP20 (CBP80/20) and typically has at least one exon junction complex (EJC) situated downstream of the nonsense codon and added post-splicing. However, mammalian NMD can also target spliced mRNA lacking an EJC downstream of the nonsense codon. Here we provide evidence that this additional pathway, known as failsafe NMD, likewise seems to be restricted to CBP80/20-bound mRNA and does not detectably target its subsequently remodeled product, eIF4E-bound mRNA. Our studies, including analyses of factor dependence, reveal important shared features of the two mammalian-cell NMD pathways as well as fundamental differences between NMD in mammals and Saccharomyces cerevisiae.
AB - Nonsense-mediated mRNA decay (NMD) generally eliminates messenger RNAs that prematurely terminate translation and occurs in all eukaryotes that have been studied, although with mechanistic variations. In mammals, NMD seems to be restricted to newly synthesized mRNA that is bound by the cap-binding heterodimer CBP80-CBP20 (CBP80/20) and typically has at least one exon junction complex (EJC) situated downstream of the nonsense codon and added post-splicing. However, mammalian NMD can also target spliced mRNA lacking an EJC downstream of the nonsense codon. Here we provide evidence that this additional pathway, known as failsafe NMD, likewise seems to be restricted to CBP80/20-bound mRNA and does not detectably target its subsequently remodeled product, eIF4E-bound mRNA. Our studies, including analyses of factor dependence, reveal important shared features of the two mammalian-cell NMD pathways as well as fundamental differences between NMD in mammals and Saccharomyces cerevisiae.
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U2 - 10.1038/nsmb1297
DO - 10.1038/nsmb1297
M3 - Article
C2 - 17873884
AN - SCOPUS:34948854852
SN - 1545-9993
VL - 14
SP - 974
EP - 979
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -