Helmholtz Gemeinschaft


Codon bias confers stability to mRNAs via ILF2 in humans

Item Type:Preprint
Title:Codon bias confers stability to mRNAs via ILF2 in humans
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 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.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:585992
Date:4 April 2019
Official Publication:https://doi.org/10.1101/585992
Related to:
https://edoc.mdc-berlin.de/18418/Final version

Repository Staff Only: item control page

Open Access
MDC Library