Biozentrum, University of Basel, 4054, Basel, Switzerland.
Mechanisms of Protein Biogenesis Laboratory, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany.
EMBO J. 2024 Nov;43(22):5747-5779. doi: 10.1038/s44318-024-00265-4. Epub 2024 Oct 14.
Embryogenesis entails dramatic shifts in mRNA translation and turnover that reprogram gene expression during cellular proliferation and differentiation. Codon identity modulates mRNA stability during early vertebrate embryogenesis, but how the composition of tRNA pools is matched to translational demand is unknown. By quantitative profiling of tRNA repertoires in zebrafish embryos during the maternal-to-zygotic transition, we show that zygotic tRNA repertoires are established after the onset of gastrulation, succeeding the major wave of zygotic mRNA transcription. Maternal and zygotic tRNA pools are distinct, but their reprogramming does not result in a better match to the codon content of the zygotic transcriptome. Instead, we find that an increase in global translation at gastrulation sensitizes decoding rates to tRNA supply, thus destabilizing maternal mRNAs enriched in slowly translated codons. Translational activation and zygotic tRNA expression temporally coincide with an increase of TORC1 activity at gastrulation, which phosphorylates and inactivates the RNA polymerase III repressor Maf1a/b. Our data indicate that a switch in global translation, rather than tRNA reprogramming, determines the onset of codon-dependent maternal mRNA decay during zebrafish embryogenesis.
胚胎发生需要在细胞增殖和分化过程中对 mRNA 翻译和周转率进行巨大的转变，以重新编程基因表达。密码子的身份在早期脊椎动物胚胎发生过程中调节 mRNA 的稳定性，但 tRNA 池的组成如何与翻译需求相匹配尚不清楚。通过对斑马鱼胚胎在母体到合子过渡期间的 tRNA 库进行定量分析，我们发现合子 tRNA 库是在原肠胚形成开始后建立的，紧随合子 mRNA 转录的主要波之后。母源和合子 tRNA 库是不同的，但它们的重编程并没有导致与合子转录组的密码子含量更好地匹配。相反，我们发现原肠胚形成时整体翻译的增加使解码率对 tRNA 供应敏感，从而使富含翻译缓慢的密码子的母体 mRNA 不稳定。翻译激活和合子 tRNA 表达与原肠胚形成时 TORC1 活性的增加同时发生，TORC1 使 RNA 聚合酶 III 抑制剂 Maf1a/b 磷酸化并使其失活。我们的数据表明，在斑马鱼胚胎发生过程中，决定依赖密码子的母体 mRNA 降解开始的是整体翻译的转变，而不是 tRNA 的重编程。
