Codon clarity or conundrum?
| Autor: | Grégory Boël, John F. Hunt, Daniel P. Aalberts |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Cell physiology Histology Gene Expression Cell Biology Computational biology Biological evolution Biology Biological Evolution Protein expression Article Pathology and Forensic Medicine law.invention 03 medical and health sciences Open reading frame Open Reading Frames 030104 developmental biology 0302 clinical medicine law Gene expression CLARITY Codon 030217 neurology & neurosurgery |
| Popis: | 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. Genome-wide RNA folding predictions confirm that natural codon choices far from the start codon are optimized in part to prevent disruption of native structures near the 5′ UTR. Our results shed light on natural codon distributions and should improve engineering of gene expression for synthetic biology applications. |
| Databáze: | OpenAIRE |
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