title: Nonsense-mediated decay targets have multiple sequence-related features that can inhibit translation.
abstract: Nonsense-mediated mRNA decay (NMD) is a surveillance system that eliminates transcripts with premature termination codons. In this study, we show that mRNAs targeted by NMD are also suppressed at the translational level. The low translational efficiency (TE) is a consequence of multiple features acting in concert, including low translation initiation rate, mediated by 5' secondary structure and by use of weak initiation sites, and low translation elongation speed, mediated by low codon usage bias. Despite low elongation rates, NMD transcripts show low ribosome density in the coding sequence, probably owing to low initiation rates, high abortion rates or rapid transit of the ribosome following initiation failure. The low TE is observed in the absence of NMD and is not explained by low transcript abundance. Translational inefficiency is flexible, such that NMD targets have increased TE upon starvation. We propose that the low TE predisposes to NMD and/or that it is part of a mechanism for regulation of NMD transcripts.
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Landian
authors.initials: L
authors.lastname: Hu
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xianfen
authors.initials: X
authors.lastname: Chen
authors.forename: Xianfu
authors.initials: X
authors.lastname: Yi
authors.forename: Xiangyin
authors.initials: X
authors.lastname: Kong
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
mesh_terms: D018389:Codon, Nonsense / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008957:Models, Genetic; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D020871:RNA Stability / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018389:Codon, Nonsense