Evidence map›Paper›PMID 41690588›Full record

ArticleThe Journal of biological chemistry2026

Human pumilio proteins use fuzzy multivalent hydrophobic interactions to recruit the CCR4-NOT deadenylase complex to repress mRNAs.

Elise B Dunshee, Brenna A Saladin, David J Turner, Chen Qiu, Robert C Dutcher, Jason G Williams, Joshua Corbo, Olivia R Wolcott, Amanda J Korte, Rebecca J Haugen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 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

13 authors.

Elise B DunsheeDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Brenna A SaladinDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
David J TurnerRNA Biology Laboratory, National Cancer Institute, NIH, Frederick, Maryland, USA.
Chen QiuEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, NIH, North Carolina, USA.
Robert C DutcherEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, NIH, North Carolina, USA.
Jason G WilliamsEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, NIH, North Carolina, USA.
Joshua CorboRNA Biology Laboratory, National Cancer Institute, NIH, Frederick, Maryland, USA.
Olivia R WolcottDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Amanda J KorteDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Rebecca J HaugenDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Traci M Tanaka HallEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, NIH, North Carolina, USA.
Eugene ValkovRNA Biology Laboratory, National Cancer Institute, NIH, Frederick, Maryland, USA.
Aaron C GoldstrohmDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address: agoldstr@umn.edu.

Funding

TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
Translational Control by Human Pumilio ProteinsR01GM150468 · NIGMS · UNIVERSITY OF MINNESOTA · PI Aaron Charles Goldstrohm · 2023 to 2026
$1.7M
NCI NIH HHS T32 CA009138NIGMS NIH HHS R01 GM150468
6 · The paper itself

Abstract

Pumilio proteins are conserved RNA-binding proteins that control mRNAs involved in development, proliferation, and differentiation. Human PUM1 and PUM2 repress targets by recruiting the CCR4-NOT deadenylase complex through a metazoan-specific, intrinsically disordered repression domain (RD3). Here we dissect RD3 using functional assays, protein interaction assays, and crosslinking mass spectrometry. We identify multiple RD3 peptides that are sufficient for repression and binding to the CCR4-NOT complex. Crosslinking reveals numerous mutually exclusive contacts between RD3 and CCR4-NOT, consistent with a multivalent "fuzzy" binding mode in which interactions are not defined by a single sequence or structure. Sequence scrambling shows that the linear amino acid order of RD3 is dispensable, whereas its physicochemical composition, in particular aliphatic and aromatic residues, is essential for repression and CCR4-NOT binding. These findings support a model in which multivalent interactions between intrinsically disordered regions and effector complexes, governed by amino acid composition, underlie robust PUM-mediated repression and exemplify general principles by which intrinsically disordered regions recruit CCR4-NOT to regulate gene expression.

Indexed as

Receptors, CCR4RibonucleasesRNA-Binding ProteinsRNA, MessengerHumansHydrophobic and Hydrophilic InteractionsProtein BindingCCR4 protein, humanPUM1 protein, humanPUM2 protein, humanReceptors, CCR4RibonucleasesRNA-Binding ProteinsRNA, MessengerCCR4–NOTgene expressionintrinsically disordered regionmRNApost-transcriptional regulationPUMRNA-binding protein

Identifiers

PMID41690588
PMCPMC12993204

What OpenQuestion holds

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LicenceCC BY-NC-ND
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 OpenQuestion graph.