Ribosomes slide on lysine-encoding homopolymeric A stretches

Kristin S. Koutmou, Anthony P. Schuller, Julie L. Brunelle, Aditya Radhakrishnan, Sergej Djuranovic, Rachel Green

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournaleLife
Volume2015
Issue number4
DOIs
StatePublished - Feb 19 2015

Fingerprint

Ribosomes
Codon
Lysine
Proteins
Messenger RNA
Bioinformatics
Transfer RNA
Nonsense Mediated mRNA Decay
Escherichia coli
Cell-Free System
Terminator Codon
Genes
Computational Biology
Eukaryota
Open Reading Frames
Kinetics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Koutmou, K. S., Schuller, A. P., Brunelle, J. L., Radhakrishnan, A., Djuranovic, S., & Green, R. (2015). Ribosomes slide on lysine-encoding homopolymeric A stretches. eLife, 2015(4). https://doi.org/10.7554/eLife.05534

Ribosomes slide on lysine-encoding homopolymeric A stretches. / Koutmou, Kristin S.; Schuller, Anthony P.; Brunelle, Julie L.; Radhakrishnan, Aditya; Djuranovic, Sergej; Green, Rachel.

In: eLife, Vol. 2015, No. 4, 19.02.2015.

Research output: Contribution to journalArticle

Koutmou, KS, Schuller, AP, Brunelle, JL, Radhakrishnan, A, Djuranovic, S & Green, R 2015, 'Ribosomes slide on lysine-encoding homopolymeric A stretches', eLife, vol. 2015, no. 4. https://doi.org/10.7554/eLife.05534
Koutmou KS, Schuller AP, Brunelle JL, Radhakrishnan A, Djuranovic S, Green R. Ribosomes slide on lysine-encoding homopolymeric A stretches. eLife. 2015 Feb 19;2015(4). https://doi.org/10.7554/eLife.05534
Koutmou, Kristin S. ; Schuller, Anthony P. ; Brunelle, Julie L. ; Radhakrishnan, Aditya ; Djuranovic, Sergej ; Green, Rachel. / Ribosomes slide on lysine-encoding homopolymeric A stretches. In: eLife. 2015 ; Vol. 2015, No. 4.
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