# Ribosomes slide on lysine-encoding homopolymeric A stretches

Article · Koutmou KS, Schuller AP, Brunelle JL, Radhakrishnan A, Djuranovic S, Green R

- Archive id: doi:10.7554/elife.05534
- Published: 2015-02-19
- Venue: eLife
- DOI: https://doi.org/10.7554/elife.05534
- PMID: 25695637
- PMCID: PMC4363877
- Citations: 104
- Source URL: https://doi.org/10.7554/elife.05534
- PDF: https://europepmc.org/articles/PMC4363877/pdf
- Provenance: europepmc

## Abstract

Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertion of synonymous AAG codons. Kinetic studies in E. coli reveal that differential protein production results from pausing on consecutive AAA-lysines followed by ribosome sliding on homopolymeric A sequence. Translation in a cell-free expression system demonstrates that diminished output from AAA-codon-containing reporters results from premature translation termination on out of frame stop codons following ribosome sliding. In eukaryotes, these premature termination events target the mRNAs for Nonsense-Mediated-Decay (NMD). The finding that ribosomes slide on homopolymeric A sequences explains bioinformatic analyses indicating that consecutive AAA codons are under-represented in gene-coding sequences. Ribosome 'sliding' represents an unexpected type of ribosome movement possible during translation.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Synthetic Biology & Genome Engineering](https://space-kitty.com/topics/synthetic-biology)

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