Evidence map›Paper›PMID 42673957›Full record

ArticleMolecular cell2026

Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.

Amoldeep S Kainth, Pallavi Sirjoosingh, Michael S Werner, Ankit Gupta, Akiko Koide, Shohei Koide, Alexander J Ruthenburg

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Amoldeep S KainthDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA.
Pallavi SirjoosinghDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.
Michael S WernerDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA.
Ankit GuptaPerlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA; Department of Medicine, New York University School of Medicine, New York, NY, USA.
Akiko KoidePerlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA; Department of Medicine, New York University School of Medicine, New York, NY, USA.
Shohei KoidePerlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA; Department of Medicine, New York University School of Medicine, New York, NY, USA.
Alexander J RuthenburgDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA. Electronic address: aruthenburg@uchicago.edu.

Funding

Defining the mechanisms of epigenetic information flowR35GM145373 · NIGMS · UNIVERSITY OF CHICAGO · PI Alexander Jackson Ruthenburg · 2022 to 2026
$2.1M
Genetically encoded designer inhibitors for functional epigenomicsR01DA036887 · NIDA · UNIVERSITY OF CHICAGO · PI KOIDE, SHOHEI · 2013 to 2017
$2.0M
Quantitatively probing intra-nucleosomal chromatin variation and functionR01GM115945 · NIGMS · UNIVERSITY OF CHICAGO · PI RUTHENBURG, ALEXANDER JACKSON · 2016 to 2020
$1.6M
Defining the role of RNA binding by the MLL1 (KMT2A) complex in leukemiaR01CA310146 · NCI · UNIVERSITY OF CHICAGO · PI Yali Dou, Alexander Jackson Ruthenburg · 2026 to 2026
$548k
NCI NIH HHS R01 CA310146NIDA NIH HHS R01 DA036887NIGMS NIH HHS R01 GM115945NIGMS NIH HHS R35 GM145373
6 · The paper itself

Abstract

Chromatin-modifying complexes are critical in gene regulation, yet their proposed interactions with RNA remain poorly understood. Counter to prior models of specific recruitment, we find that WDR5, an essential subunit of the MLL1/KMT2A histone methyltransferase complex, binds RNA promiscuously. Using a stringent approach, we demonstrate that WDR5 directly engages a diverse pool of cellular RNAs, dictated primarily by RNA abundance rather than specific motifs. Equilibrium binding assays show that RNA length, rather than sequence, governs high affinity. WDR5 binds to RNA through multiple surfaces, some of which overlap with MLL1 complex subunit interfaces. Strikingly, we find that RNA binding disrupts the MLL1 complex by competitively displacing WDR5 from these critical protein-protein interactions, leading to a marked inhibition of MLL1 catalytic activity. Further experiments in human cell lines suggest that this disassembly mechanism may operate to homeostatically downregulate MLL1 complex activity, thereby integrating transcriptional activity with chromatin state.

Indexed as

Histone-Lysine N-MethyltransferaseIntracellular Signaling Peptides and ProteinsMyeloid-Lymphoid Leukemia ProteinRNABinding SitesChromatinHEK293 CellsHistonesHumansProtein BindingTranscription, GeneticChromatinHistone-Lysine N-MethyltransferaseHistonesIntracellular Signaling Peptides and ProteinsKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinRNAWDR5 protein, humanchromatinH3K4me3KMT2A (MLL1)MLLPAR-CRACRNA-binding proteintranscriptionWDR5

Identifiers

PMID42673957
PMCPMC13533456

What Socratic holds

Textmetadata
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 Socratic graph.