Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition.
Cellular transitions require dramatic changes in gene expression that are supported by regulated mRNA decay and new transcription. The maternal-to-zygotic transition is a conserved developmental progression during which thousands of maternal mRNAs are cleared by post-transcriptional mechanisms. Although some maternal mRNAs are targeted for degradation by microRNAs, this pathway does not fully explain mRNA clearance. We investigated how codon identity and translation affect mRNA stability during development and homeostasis. We show that the codon triplet contains translation-dependent regulatory information that influences transcript decay. Codon composition shapes maternal mRNA clearance during the maternal-to-zygotic transition in zebrafish, Xenopus, mouse, and Drosophila, and gene expression during homeostasis across human tissues. Some synonymous codons show consistent stabilizing or destabilizing effects, suggesting that amino acid composition influences mRNA stability. Codon composition affects both polyadenylation status and translation efficiency. Thus, the ribosome interprets two codes within the mRNA: the genetic code which specifies the amino acid sequence and a conserved "codon optimality code" that shapes mRNA stability and translation efficiency across vertebrates.
['Bazzini|Ariel A|AA|', 'Del Viso|Florencia|F|', 'Moreno-Mateos|Miguel A|MA|', 'Johnstone|Timothy G|TG|', 'Vejnar|Charles E|CE|', 'Qin|Yidan|Y|', 'Yao|Jun|J|', 'Khokha|Mustafa K|MK|', 'Giraldez|Antonio J|AJ|0000-0002-2251-5174']
D000818:Animals D003062:Codon D004330:Drosophila D005786:Gene Expression Regulation D006801:Humans D051379:Mice D014176:Protein Biosynthesis D020871:RNA Stability D012333:RNA, Messenger D012270:Ribosomes D014981:Xenopus D015027:Zebrafish D015053:Zygote
translation decay zebrafish codon optimality maternal‐to‐zygotic transition