Codon bias confers stability to mRNAs via ILF2 in humans

Item Type:

Preprint

Title:

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.

Source:

bioRxiv

Publisher:

Cold Spring Harbor Laboratory Press

Article Number:

585992

Date:

4 April 2019

Official Publication:

https://doi.org/10.1101/585992

Related to:

URL	URL Type
https://edoc.mdc-berlin.de/18418/	Final version

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