Evidence map›Paper›PMID 41958995›Full record

ArticlebioRxiv : the preprint server for biology2026

A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.

Jie Liu, Megan K Moore, Kevin Lou, Douglas R Wassarman, Abolfazl Arab, Samuel Ojeda, Barbara Karakyriakou, Ann-Sophie Koglin, Christopher J Ott, Luke A Gilbert and 1 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

5 · Who and what money

Authors and funding

11 authors.

Jie LiuDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-9455-325X
Megan K MooreDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Kevin LouDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Douglas R WassarmanDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Abolfazl ArabDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Samuel OjedaMassachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Barbara KarakyriakouMassachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.ORCID 0000-0001-7820-2567
Ann-Sophie KoglinMassachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Christopher J OttMassachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Luke A GilbertHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-5854-0825
Kevan M ShokatDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-8590-7741

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI James Solomon Fraser · 2022 to 2026
$103.4M
Mechanisms and models of C11or95 and C11or95-RELA fusions (RELAFus )U54CA243125 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HOLLAND, ERIC C. · 2019 to 2022
$6.2M
Research Training in Chemistry and Chemical BiologyT32GM145460 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jason E Gestwicki · 2022 to 2026
$3.1M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
Wide field-of-view Spinning Disk Confocal with Photoactivation and PhotobleachingS10OD017993 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI THORN, KURT · 2015 to 2015
$274k
NCI NIH HHS U54 CA243125NIAID NIH HHS U19 AI171110NIGMS NIH HHS T32 GM145460NIH HHS S10 OD017993NIH HHS S10 OD028511
6 · The paper itself

Abstract

Ligand dimerization represents a powerful strategy to enhance avidity, potency, and selectivity. Leveraging the natural-product molecular glue Rocaglamide (RocA), we identified BisRoc, a dimeric rocaglate ligand that potently and durably suppresses translation and exhibits greater specificity across a cancer cell line panel than the monomeric RocA. CRISPRi screening revealed that BisRoc activity is influenced by cellular context, including IFITM-mediated uptake, ABC-type efflux transporters, and the translation initiation factor eIF4A2. Mechanistic studies showed that the paralogs eIF4A1 and eIF4A2 are differentially sensitive to BisRoc-induced dimerization. Owing to the presence of multiple binding sites on RNAs, BisRoc-bridged eIF4A-RNA motifs assemble into higher-order complexes that promote stress-granule formation more efficiently than monomeric RocA. Given the widespread multivalency of RNA-RBP interactions, this ligand dimerization strategy may be extended to modulate the higher-order assembly of other RNA-binding proteins.

Identifiers

PMID41958995
PMCPMC13060801

What OpenQuestion holds

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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.