西亚试剂：Nonsense-mediated decay targets have multiple sequence-rela

Nonsense-mediated decay targets have multiple sequence-related features that can inhibit translation

Zhenguo Zhang1,2,a, Li Zhou1,2, Landian Hu1, Yufei Zhu1, Heng Xu1,2, Yang Liu1,2, Xianfen Chen1,2, Xianfu Yi1,2, Xiangyin Kong1,3 & Laurence D Hurst4

The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, PR China

Graduate School of the Chinese Academy of Sciences, Beijing, PR China

State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, PR China

Department of Biology and Biochemistry, University of Bath, Bath, UK

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.