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Codon bias confers stability to human mRNAs

Item Type:Article
Title:Codon bias confers stability to human mRNAs
Creators Name:Hia, F. and Yang, S.F. and Shichino, Y. and Yoshinaga, M. and Murakawa, Y. and Vandenbon, A. and Fukao, A. and Fujiwara, T. and Landthaler, M. and Natsume, T. and Adachi, S. and Iwasaki, S. and Takeuchi, O.
Abstract:Codon bias has been implicated as one of the major factors contributing to mRNA stability in several model organisms. However, the molecular mechanisms of codon bias on mRNA stability remain unclear in humans. Here, we show that human cells possess a mechanism to modulate RNA stability through a unique codon bias. Bioinformatics analysis showed that codons could be clustered into two distinct groups-codons with G or C at the third base position (GC3) and codons with either A or T at the third base position (AT3): the former stabilizing while the latter destabilizing mRNA. Quantification of codon bias showed that increased GC3-content entails proportionately higher GC-content. Through bioinformatics, ribosome profiling, and in vitro analysis, we show that decoupling the effects of codon bias reveals two modes of mRNA regulation, one GC3- and one GC-content dependent. Employing an immunoprecipitation-based strategy, we identify ILF2 and ILF3 as RNA-binding proteins that differentially regulate global mRNA abundances based on codon bias. Our results demonstrate that codon bias is a two-pronged system that governs mRNA abundance.
Keywords:Codon Bias, Codon Optimality, GC-Content, mRNA Stability, Translation Efficiency
Source:EMBO Reports
ISSN:1469-221X
Publisher:EMBO Press (U.K.)
Volume:20
Number:11
Page Range:e48220
Date:5 November 2019
Official Publication:https://doi.org/10.15252/embr.201948220
PubMed:View item in PubMed
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https://edoc.mdc-berlin.de/18180/Preprint version

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