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Transient ribosome slowdown at the decoding step triggers mRNA degradation independent of Znf598 in zebrafish

View ORCID ProfileYuichiro Mishima, Peixun Han, View ORCID ProfileSeisuke Kimura, View ORCID ProfileShintaro Iwasaki
doi: https://doi.org/10.1101/2021.05.12.443743
Yuichiro Mishima
1Department of Frontier Life Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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  • For correspondence: mishima@cc.kyoto-su.ac.jp
Peixun Han
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
3Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan
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Seisuke Kimura
4Department of Industrial Life Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
5Center for Plant Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
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Shintaro Iwasaki
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
3Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan
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Abstract

The control of mRNA stability plays a central role in regulating gene expression patterns. Recent studies have revealed that codon composition in the open reading frame (ORF) determines mRNA stability in multiple organisms. Based on genome-wide correlation approaches, this previously unrecognized role of the genetic code is attributable to the kinetics of the codon-decoding process by the ribosome. However, complementary experimental analysis is required to define the codon effects on mRNA stability apart from the related cotranslational mRNA decay pathways such as those triggered by aberrant ribosome stalls. In the current study, we performed a set of reporter-based analyses to define codon-mediated mRNA decay and ribosome stall-dependent mRNA decay in zebrafish embryos. Our analysis showed that the effect of codons on mRNA stability stems from the decoding process, independent of Znf598 and stall-dependent mRNA decay. We propose that codon-mediated mRNA decay is triggered by transiently slowed ribosomes engaging in a productive translation cycle in zebrafish embryos.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 14, 2021.
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Transient ribosome slowdown at the decoding step triggers mRNA degradation independent of Znf598 in zebrafish
Yuichiro Mishima, Peixun Han, Seisuke Kimura, Shintaro Iwasaki
bioRxiv 2021.05.12.443743; doi: https://doi.org/10.1101/2021.05.12.443743
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Transient ribosome slowdown at the decoding step triggers mRNA degradation independent of Znf598 in zebrafish
Yuichiro Mishima, Peixun Han, Seisuke Kimura, Shintaro Iwasaki
bioRxiv 2021.05.12.443743; doi: https://doi.org/10.1101/2021.05.12.443743

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