Translation initiation downstream from annotated start codons in human mRNAs coevolves with the Kozak context.

Genome Research
Maria S Benitez-CantosPavel V Baranov

Abstract

Eukaryotic translation initiation involves preinitiation ribosomal complex 5'-to-3' directional probing of mRNA for codons suitable for starting protein synthesis. The recognition of codons as starts depends on the codon identity and on its immediate nucleotide context known as Kozak context. When the context is weak (i.e., nonoptimal), leaky scanning takes place during which a fraction of ribosomes continues the mRNA probing. We explored the relationship between the context of AUG codons annotated as starts of protein-coding sequences and the next AUG codon occurrence. We found that AUG codons downstream from weak starts occur in the same frame more frequently than downstream from strong starts. We suggest that evolutionary selection on in-frame AUGs downstream from weak start codons is driven by the advantage of the reduction of wasteful out-of-frame product synthesis and also by the advantage of producing multiple proteoforms from certain mRNAs. We confirmed translation initiation downstream from weak start codons using ribosome profiling data. We also tested translation of alternative start codons in 10 specific human genes using reporter constructs. In all tested cases, initiation at downstream start codons was more produc...Continue Reading

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Citations

Feb 19, 2021·Nature Communications·Hong ZhangJian Lu
Jun 18, 2021·The Journal of Physical Chemistry Letters·Wenxin WangJie Jiang
Sep 8, 2021·Frontiers in Cell and Developmental Biology·Oza ZaheedKellie Dean

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