Ribosome slowdown triggers codon‐mediated mRNA decay independently of ribosome quality control
- 18 January 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 41 (5), e109256
- https://doi.org/10.15252/embj.2021109256
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 determines mRNA stability in multiple organisms. Based on genome-wide correlation approaches, this previously unrecognized role for the genetic code is attributable to the kinetics of the codon-decoding process by the ribosome. However, complementary experimental analyses are required to clarify the codon effects on mRNA stability and the related cotranslational mRNA decay pathways, for example, those triggered by aberrant ribosome stalling. 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 the ribosome quality control factor Znf598 and stalling-dependent mRNA decay. We propose that codon-mediated mRNA decay is rather triggered by transiently slowed ribosomes engaging in a productive translation cycle in zebrafish embryos.Keywords
Funding Information
- Japan Society for the Promotion of Science (JP18H02370)
- RIKEN
- Takeda Science Foundation
- Japan Society for the Promotion of Science (JP21H02513)
- Ministry of Education, Culture, Sports, Science and Technology (S1511023)
- Ministry of Education, Culture, Sports, Science and Technology (JP17H05593)
- Ministry of Education, Culture, Sports, Science and Technology (JP17H05662)
- Japan Agency for Medical Research and Development (JP21gm6310017)
- Japan Society for the Promotion of Science (JP17H04998)
- Japan Society for the Promotion of Science (JP19K22406)
- Ministry of Education, Culture, Sports, Science and Technology (JP20H05784)
- Japan Agency for Medical Research and Development (JP21gm1410001)
- Inamori Foundation
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