RT Journal Article
SR Electronic
T1 Codon Bias Confers Stability to mRNAs via ILF2 in Humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 585992
DO 10.1101/585992
A1 Fabian Hia
A1 Sheng Fan Yang
A1 Yuichi Shichino
A1 Masanori Yoshinaga
A1 Yasuhiro Murakawa
A1 Alexis Vandenbon
A1 Akira Fukao
A1 Toshinobu Fujiwara
A1 Markus Landthaler
A1 Tohru Natsume
A1 Shungo Adachi
A1 Shintaro Iwasaki
A1 Osamu Takeuchi
YR 2019
UL http://biorxiv.org/content/early/2019/04/04/585992.abstract
AB Codon bias has been implicated as one of the major factors contributing to mRNA stability in yeast. However, the effects 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 different from that of yeast. 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 of the effects of codon bias reveals two modes of mRNA regulation, GC3- and GC-content dependent. Employing an immunoprecipitation-based strategy, we identified ILF2 as an RNA binding protein that differentially regulates global mRNA abundances based on codon bias. Our results demonstrate that codon bias is a two-pronged system that governs mRNA abundance.