Evidence map›Paper›PMID 35528200›Full record

ArticleNAR cancer2022

Integrative genome-wide analysis reveals EIF3A as a key downstream regulator of translational repressor protein Musashi 2 (MSI2).

Shilpita Karmakar, Oscar Ramirez, Kiran V Paul, Abhishek K Gupta, Vandana Kumari, Valentina Botti, Igor Ruiz de Los Mozos, Nils Neuenkirchen, Robert J Ross, John Karanicolas and 2 more

Open access · goldAbstract read
In one paragraph

Article in NAR cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

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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 at 4 institutions in 2 countries.

Shilpita KarmakarSection of Hematology, Yale Cancer Center, New Haven, CT 06511, USA.
Oscar RamirezSection of Hematology, Yale Cancer Center, New Haven, CT 06511, USA.
Kiran V PaulSection of Hematology, Yale Cancer Center, New Haven, CT 06511, USA.
Abhishek K GuptaSection of Hematology, Yale Cancer Center, New Haven, CT 06511, USA.
Vandana KumariSection of Hematology, Yale Cancer Center, New Haven, CT 06511, USA.
Valentina BottiDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510, USA.
Igor Ruiz de Los MozosInstitute of Neurology, University College London and The Francis Crick Institute, London NW1 1AT, UK.ORCID https://orcid.org/0000-0003-4097-6422
Nils NeuenkirchenDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06511, USA.
Robert J RossDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06511, USA.
John KaranicolasProgram in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Karla M NeugebauerDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510, USA.
Manoj M PillaiSection of Hematology, Yale Cancer Center, New Haven, CT 06511, USA.ORCID https://orcid.org/0000-0002-7835-0145
Yale Cancer Center · USYale University · USFox Chase Cancer Center · USThe Francis Crick Institute · GB

Funding

Yale Cooperative Hematology Specialized Core CenterU54DK106857 · NIDDK · YALE UNIVERSITY · PI JOHN HWA, Diane S Krause · 2015 to 2026
$9.7M
Robust Rational Design of Chemical Tools to Inhibit RNA-binding ProteinsR01GM123336 · NIGMS · RESEARCH INST OF FOX CHASE CAN CTR · PI KARANICOLAS, JOHN · 2017 to 2020
$1.5M
NIDDK NIH HHS U54 DK106857NIGMS NIH HHS R01 GM123336
6 · The paper itself

Abstract

Musashi 2 (MSI2) is an RNA binding protein (RBP) that regulates asymmetric cell division and cell fate decisions in normal and cancer stem cells. MSI2 appears to repress translation by binding to 3' untranslated regions (3'UTRs) of mRNA, but the identity of functional targets remains unknown. Here, we used individual nucleotide resolution cross-linking and immunoprecipitation (iCLIP) to identify direct RNA binding partners of MSI2 and integrated these data with polysome profiling to obtain insights into MSI2 function. iCLIP revealed specific MSI2 binding to thousands of mRNAs largely in 3'UTRs, but translational differences were restricted to a small fraction of these transcripts, indicating that MSI2 regulation is not triggered by simple binding. Instead, the functional targets identified here were bound at higher density and contain more 'UAG' motifs compared to targets bound nonproductively. To further distinguish direct and indirect targets, MSI2 was acutely depleted. Surprisingly, only 50 transcripts were found to undergo translational induction on acute loss. Using complementary approaches, we determined eukaryotic translation initiation factor 3A (EIF3A) to be an immediate, direct target. We propose that MSI2 downregulation of EIF3A amplifies these effects on translation. Our results also underscore the challenges in defining functional targets of RBPs since mere binding does not imply a discernible functional interaction.

Identifiers

PMID35528200
PMCPMC9070473
OpenAlexW4229071684

What Socratic 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 Socratic graph.