title: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition.
abstract: 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.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA Stowers Institute for Medical Research, Kansas City, MO, USA arb@stowers.org antonio.giraldez@yale.edu.
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Bazzini
authors.affiliation: Departments of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Florencia
authors.initials: F
authors.lastname: Del Viso
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Moreno-Mateos
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Johnstone
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Vejnar
authors.affiliation: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA Departments of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Mustafa K
authors.initials: MK
authors.lastname: Khokha
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA arb@stowers.org antonio.giraldez@yale.edu.
authors.forename: Antonio J
authors.identifier: 0000-0002-2251-5174
authors.initials: AJ
authors.lastname: Giraldez
mesh_terms: D000818:Animals; D003062:Codon; D004330:Drosophila; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism; D014981:Xenopus; D015027:Zebrafish; D015053:Zygote / Q000254:growth & development*
chemical_list: D003062:Codon; D012333:RNA, Messenger
keywords: codon optimality; decay; maternal‐to‐zygotic transition; translation; zebrafish