Open AccessEvolutionarily conserved inhibitory uORFs sensitize Hox mRNA translation to start codon selection stringency
Author(s) -
Ivaylo P. Ivanov,
James A. Saba,
ChenMing Fan,
Ji Wang,
Andrew E. Firth,
Chune Cao,
Rachel Green,
Thomas E. Dever
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2117226119
Subject(s) - biology , start codon , hox gene , genetics , ribosomal binding site , shine dalgarno sequence , eukaryotic translation , gene , translation (biology) , stop codon , codon usage bias , ribosome , open reading frame , context (archaeology) , conserved sequence , messenger rna , gene expression , rna , peptide sequence , genome , paleontology
Significance Cellular protein synthesis relies on faithful selection of the translation start codon by the ribosome. Initiation at alternative sites on a messenger RNA (mRNA) impairs production of native proteins, triggers synthesis of junk proteins, and enables regulation of translation. The nucleotide sequence flanking a start codon controls its efficiency of selection. We identify mRNAs containing start codons in conserved poor sequence contexts, including severalHox mRNAs encoding regulators of the body plan. OtherHox mRNAs contain conserved upstream open reading frames with poor start codon contexts that sensitize translation to changes in start codon selection stringency. Thus, alterations in start codon selection stringency has the potential to regulate global gene expression programs, includingHox gene-directed body plan formation in animals.