Article abstract
Nature Structural & Molecular Biology 14, 974 - 979 (2007)
Published online: 16 September 2007 | doi:10.1038/nsmb1297
Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA
Daiki Matsuda1,3, Nao Hosoda1,2,3, Yoon Ki Kim1,2 & Lynne E Maquat1
Abstract
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.
- Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA.
- Present addresses: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan (N.H.), and School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-701, Republic of Korea (Y.K.K.).
- These authors contributed equally to this work.
Correspondence to: Lynne E Maquat1 e-mail: lynne_maquat@urmc.rochester.edu
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