Multifaceted Regulation of Translationally Challenging mRNAs in Zebrafish

 

Yuichiro Mishima, Ph.D.

Professor, Faculty of Lifesciences, Kyoto Sangyo University

 

Translation is a fundamental process for producing the vast array of proteins required in the cell, and it is mediated exclusively by the ribosome. To fulfill this role, the ribosome must be capable of translating a wide variety of mRNA and peptide sequences. In reality, however, ribosomes often slow down, stall, or even collide with one another on mRNAs that encode sequences difficult to translate. Such translational challenges are not only detrimental to cells but can also serve as cues for regulating gene expression.

   We have been investigating two such examples using zebrafish as an in vivo model system. In one case, a transient slowdown of ribosomes caused by low tRNA availability induces rapid mRNA decay after fertilization. In another case, aberrant ribosome stalling and collisions at difficult-to-translate sequences are detected by the cellular quality control machinery, leading to mRNA degradation. Our genome-wide translational profiling and reporter assays revealed that each pathway targets distinct classes of mRNAs, each presenting unique translational challenges.

   In this seminar, I will introduce these multifaceted regulatory mechanisms of translationally challenging mRNAs and discuss how ribosome-mediated mRNA regulation shapes and safeguards gene expression programs during animal development.

 

References

Ishibashi K et al., Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish. PLoS Biol. 2024 Dec 5;22(12):e3002887.

 

Mishima Y et al., Ribosome slowdown triggers codon-mediated mRNA decay independently of ribosome quality control. EMBO J. 2022 Mar 1;41(5):e109256.

 

Mishima Y and Tomari Y. Codon Usage and 3′ UTR Length Determine Maternal mRNA Stability in Zebrafish. Mol Cell. 2016 Mar 17;61(6):874-85.