RNA Structural Determinants of Optimal Codons Revealed by MAGE-Seq.

ABSTRACT: Synonymous codon choices at the beginning of genes optimize 5' RNA structures for enhanced translation initiation, but less is known about mechanisms that drive codon optimization downstream within the gene. To understand what determines codon choices across a gene, we generated 12,726 in situ codon mutants in the Escherichia coli essential gene infA and measured their fitness by combining multiplex automated genome engineering mutagenesis with amplicon deep sequencing (MAGE-seq). Correlating predicted 5' RNA structure with fitness revealed that codons even far from the start of the gene are deleterious if they disrupt the native 5' RNA conformation. These long-range structural interactions generate context-dependent rules that constrain codon choices beyond intrinsic codon preferences. Ge

SUBMITTER: Kelsic ED 

PROVIDER: S-EPMC5234859 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature