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Codon Bias Confers Stability to mRNAs via ILF2 in Humans

View ORCID ProfileFabian Hia, Sheng Fan Yang, Yuichi Shichino, Masanori Yoshinaga, Yasuhiro Murakawa, Alexis Vandenbon, Akira Fukao, Toshinobu Fujiwara, Markus Landthaler, Tohru Natsume, Shungo Adachi, Shintaro Iwasaki, View ORCID ProfileOsamu Takeuchi
doi: https://doi.org/10.1101/585992
Fabian Hia
1Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
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  • ORCID record for Fabian Hia
Sheng Fan Yang
1Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
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Yuichi Shichino
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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Masanori Yoshinaga
1Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
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Yasuhiro Murakawa
3Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Yokohama, Kanagawa 230-0045, Japan
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Alexis Vandenbon
4Laboratory of Infection and Prevention, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan
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Akira Fukao
5Laboratory of Biochemistry, Department of Pharmacy, Kindai University, Higashiosaka City, Osaka, 577-8502 Japan
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Toshinobu Fujiwara
5Laboratory of Biochemistry, Department of Pharmacy, Kindai University, Higashiosaka City, Osaka, 577-8502 Japan
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Markus Landthaler
6RNA Biology and Posttranscriptional Regulation, Max Delbrück Center for Molecular Medicine Berlin, Berlin Institute for Molecular Systems Biology, 13125 Berlin, Germany; IRI Life Sciences, Institut für Biologie, Humboldt-Universität zu Berlin, 10115 Berlin, Germany
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Tohru Natsume
7Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo 135-0064, Japan
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Shungo Adachi
7Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo 135-0064, Japan
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Shintaro Iwasaki
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
8Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan
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Osamu Takeuchi
1Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
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  • ORCID record for Osamu Takeuchi
  • For correspondence: otake@mfour.med.kyoto-u.ac.jp
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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.

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Posted April 04, 2019.
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Codon Bias Confers Stability to mRNAs via ILF2 in Humans
Fabian Hia, Sheng Fan Yang, Yuichi Shichino, Masanori Yoshinaga, Yasuhiro Murakawa, Alexis Vandenbon, Akira Fukao, Toshinobu Fujiwara, Markus Landthaler, Tohru Natsume, Shungo Adachi, Shintaro Iwasaki, Osamu Takeuchi
bioRxiv 585992; doi: https://doi.org/10.1101/585992
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Codon Bias Confers Stability to mRNAs via ILF2 in Humans
Fabian Hia, Sheng Fan Yang, Yuichi Shichino, Masanori Yoshinaga, Yasuhiro Murakawa, Alexis Vandenbon, Akira Fukao, Toshinobu Fujiwara, Markus Landthaler, Tohru Natsume, Shungo Adachi, Shintaro Iwasaki, Osamu Takeuchi
bioRxiv 585992; doi: https://doi.org/10.1101/585992

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