Evidence map›Paper›PMID 25695637›Full record

ArticleeLife2015

Ribosomes slide on lysine-encoding homopolymeric A stretches.

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

Open access · goldAbstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Transfer RNA acetylation regulates in vivo mammalian stress signaling.bioRxiv : the preprint server for biology · 2024
    Article
  15. Translation Rates and Protein Folding.Journal of molecular biology · 2024
    Review
  16. Article
  17. Article
  18. Systematic analysis of nonprogrammed frameshift suppression inProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Review
  20. Article

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Kristin S KoutmouDepartment of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States.
Anthony P SchullerDepartment of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States.
Julie L BrunelleDepartment of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States.
Aditya RadhakrishnanDepartment of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States.
Sergej DjuranovicDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, United States.
Rachel GreenDepartment of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States.
Johns Hopkins University · USJohns Hopkins Medicine · USWashington University in St. Louis · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Molecular mechanisms of ribosome pausing and the cellular responseR37GM059425 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 2014 to 2023
$3.5M
MECHANISMS FOR MODULATION OF MIRNA-MEDIATED GENE SILENCINGR01GM112824 · NIGMS · WASHINGTON UNIVERSITY · PI DJURANOVIC, SERGEJ · 2015 to 2023
$3.1M
Mechanism and targets of non-stop decay in eukaryotic translationF32GM100608 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KOUTMOU, KRISTIN S · 2012 to 2014
$169k
Howard Hughes Medical InstituteNIGMS NIH HHS F32 GM100608NIGMS NIH HHS R01 GM112824NIGMS NIH HHS R37 GM059425NIGMS NIH HHS T32 GM007445
6 · The paper itself

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.

Indexed as

Base SequenceBlotting, WesternCodonEscherichia coliGene DeletionLuminescent ProteinsLysineMolecular Sequence DataPoly AProtein BiosynthesisRed Fluorescent ProteinReverse Transcriptase Polymerase Chain ReactionRibosomesRNA HelicasesRNA, MessengerRNA StabilityCodonLuminescent ProteinsLysineNAM7 protein, S cerevisiaePoly ARed Fluorescent ProteinRNA HelicasesRNA, MessengerSaccharomyces cerevisiae ProteinsbiochemistryE. colipoly(A)ribosomeS. cerevisiaesliding

Identifiers

PMID25695637
PMCPMC4363877
OpenAlexW2120595470

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.