Evidence map›Paper›PMID 40721534›Full record

ArticleNature structural & molecular biology2025

eIF1 and eIF5 dynamically control translation start site fidelity.

Rosslyn Grosely, Carlos Alvarado, Ivaylo P Ivanov, Oliver B Nicholson, Joseph D Puglisi, Thomas E Dever, Christopher P Lapointe

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Remodeling of mRNA by eIF4F in human translation initiation.bioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Structural insights into the role of eIF3 in translation mediated by the HCV IRES.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Dynamics and Regulation of mRNA Cap Recognition by Human eIF4F.bioRxiv : the preprint server for biology · 2025
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Rosslyn Grosely *Dept. of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Carlos Alvarado *Dept. of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Ivaylo P IvanovEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Oliver B NicholsonBasic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Joseph D PuglisiDept. of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-9268-5112
Thomas E DeverEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. thomas.dever@nih.gov.ORCID http://orcid.org/0000-0001-7120-9678
Christopher P LapointeBasic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. cplapointe@fredhutch.org.ORCID http://orcid.org/0000-0002-0406-105X

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Dynamics of TranslationR35GM145306 · NIGMS · STANFORD UNIVERSITY · PI JOSEPH D PUGLISI · 2022 to 2026
$3.8M
Defining modifiers and mechanisms of RAN translationRF1AG064690 · NIA · STANFORD UNIVERSITY · PI GITLER, AARON D., PUGLISI, JOSEPH D · 2019 to 2019
$2.8M
Defining modifiers and mechanisms of RAN translationR01AG064690 · NIA · STANFORD UNIVERSITY · PI Aaron D. Gitler, JOSEPH D PUGLISI · 2024 to 2026
$2.3M
Defining mechanisms that underlie well-controlled translation initiationR35GM160398 · NIGMS · FRED HUTCHINSON CANCER CENTER · PI Christopher Paul Lapointe · 2025 to 2026
$968k
From one end to the other: dynamics of human translation initiation and its controlR00GM144678 · NIGMS · FRED HUTCHINSON CANCER CENTER · PI LAPOINTE, CHRISTOPHER PAUL · 2023 to 2024
$498k
From one end to the other: dynamics of human translation initiation and its controlK99GM144678 · NIGMS · STANFORD UNIVERSITY · PI LAPOINTE, CHRISTOPHER PAUL · 2022 to 2023
$164k
NCI NIH HHS P30 CA015704NIA NIH HHS R01 AG064690NIA NIH HHS RF1 AG064690NIGMS NIH HHS K99 GM144678NIGMS NIH HHS R00 GM144678NIGMS NIH HHS R35 GM145306NIGMS NIH HHS R35 GM160398
6 · The paper itself

Abstract

Human translation initiation requires accurate recognition of translation start sites. While AUG codons are canonical start sites, non-AUG codons are also used, typically with lower efficiency. The initiator tRNA and initiation factors eIF1 and eIF5 control recognition. How they distinguish different start sites yet allow flexible recognition remains unclear. Here we used real-time single-molecule assays and an in vitro reconstituted human system to reveal how eIF1 and eIF5 direct start site selection. eIF1 binds initiation complexes in two modes: stable binding during scanning, followed by transient, concentration-dependent rebinding after start site recognition. Termination of eIF1 rebinding requires transient and concentration-dependent binding by eIF5, which allows the formation of translation competent ribosomes. Non-AUG start sites differentially stabilize eIF1 and destabilize eIF5 binding, blocking initiation at multiple points. We confirmed these opposing effects in human cells. Collectively, our findings uncover that eIF1 and eIF5 directly compete to bind initiation complexes and illuminate how their dynamic interplay tunes the fidelity of start site recognition, which has broad connections to health and disease.

Indexed as

Eukaryotic Initiation Factor-1Peptide Chain Initiation, TranslationalPeptide Initiation FactorsCodon, InitiatorEukaryotic Initiation FactorsEukaryotic Translation Initiation Factor 5AHumansNeoplasm ProteinsNerve Tissue ProteinsProtein BindingProtein BiosynthesisRibosomesCodon, InitiatorEIF1 protein, humanEukaryotic Initiation Factor-1Eukaryotic Initiation FactorsEukaryotic Translation Initiation Factor 5ANeoplasm ProteinsNerve Tissue ProteinsPeptide Initiation Factors

Identifiers

PMID40721534
PMCPMC12360421

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Registered trials

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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.