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Codon bias confers stability to human mRNA s
Author(s) -
Hia Fabian,
Yang Sheng Fan,
Shichino Yuichi,
Yoshinaga Masanori,
Murakawa Yasuhiro,
Vandenbon Alexis,
Fukao Akira,
Fujiwara Toshinobu,
Landthaler Markus,
Natsume Tohru,
Adachi Shungo,
Iwasaki Shintaro,
Takeuchi Osamu
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948220
Subject(s) - library science , political science , computer science
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 ( GC 3) and codons with either A or T at the third base position ( AT 3): the former stabilizing while the latter destabilizing mRNA . Quantification of codon bias showed that increased GC 3‐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 GC 3‐ and one GC ‐content dependent. Employing an immunoprecipitation‐based strategy, we identify ILF 2 and ILF 3 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.