BioProject

Cellular transitions require dramatic changes in gene expression that are supported by regulated mRNA decay and new transcription. More...

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 posttranscriptional mechanisms. Although some maternal mRNAs are targeted for degradation by microRNAs, this pathway does not fully explain mRNA clearance. Because the ribosome constitutes the main ribonucleoprotein complex decoding the mRNA, we investigated how codon identity and translation affect mRNA stability during development and homeostasis. Using an in-vivo selection strategy, we show that the codon triplet contains translation-dependent regulatory information that influences transcript decay. We find that 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. 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. Less...