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.
In addition to spelling out protein sequence, mRNA codon triplets contain translation‐dependent regulatory information that influences transcript stability and contributes to controlled turnover of maternal mRNAs in frogs, mice, and flies.
Codon optimality forms a regulatory code within the genetic code that controls mRNA stability and translation efficiency.
Codon composition shapes maternal mRNA clearance during the maternal‐to‐zygotic transition in zebrafish, frog, mouse, and fly in a translation‐dependent manner.
Amino acid composition also influences mRNA stability in vertebrates.
Codon optimality correlates with codon bias, suggesting that codon optimality shapes steady‐state mRNA levels in homeostasis.
- Received May 4, 2016.
- Revision received June 10, 2016.
- Accepted June 16, 2016.
- © 2016 The Authors
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