Evidence map›Paper›PMID 42367976›Full record

ArticlebioRxiv : the preprint server for biology2026

Remodeling of mRNA by eIF4F in human translation initiation.

Carlos Alvarado, Christopher P Lapointe, Jinfan Wang, Masaaki Sokabe, Rosslyn Grosely, Ajinkya A Dhepe, Crystal I Stackhouse, Michael Z Palo, Adam Mamot, Jacek Jemielity and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Carlos AlvaradoDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Christopher P LapointeBasic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID 0000-0002-0406-105X
Jinfan WangDepartment of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Masaaki SokabeDepartment of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, CA, USA.
Rosslyn GroselyDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Ajinkya A DhepeDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Crystal I StackhouseDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Michael Z PaloDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Adam MamotDepartment of Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Martinsried, Germany.
Jacek JemielityCentre of New Technologies, University of Warsaw, 02-089 Warsaw, Poland.
Christopher S FraserDepartment of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, CA, USA.
Joseph D PuglisiDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.

Funding

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
The mechanisms of mRNA recruitment to the human ribosomeR35GM152137 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Christopher S Fraser · 2024 to 2026
$1.3M
Defining mechanisms that underlie well-controlled translation initiationR35GM160398 · NIGMS · FRED HUTCHINSON CANCER CENTER · PI Christopher Paul Lapointe · 2025 to 2026
$968k
NIA NIH HHS R01 AG064690NIA NIH HHS RF1 AG064690NIGMS NIH HHS R35 GM145306NIGMS NIH HHS R35 GM152137NIGMS NIH HHS R35 GM160398
6 · The paper itself

Abstract

For the ribosome to load onto an mRNA during the early steps of translation initiation, the mRNA must be activated by the eIF4F complex. The mechanism of this activation step has remained elusive. Here we employ multi-perspective real-time single-molecule assays to observe directly mRNA-eIF4F binding near the 5' end, mRNA conformational remodeling, and 40S ribosomal subunit loading. eIFs 4E, 4G, and 4B play distinct roles in promoting eIF4F association and stabilizing eIF4A binding. Binding of eIF4F is the rate-limiting step in mRNA activation: once bound, mRNA conformation is rapidly extended in an ATP-dependent manner. The mRNA extended state is the necessary substrate for 43S PIC loading and perturbations to extension delay loading. Features of the mRNA, such as the 7-methylguanosine cap at the 5' end and secondary structures, modulate these steps and regulate ribosome loading. Our results establish a kinetic and mechanistic framework for the early steps in translation initiation.

Identifiers

PMID42367976
PMCPMC13308167

What Socratic holds

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LicenceCC BY
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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 Socratic graph.