Evidence map›Paper›PMID 40586305›Full record

ArticleNucleic acids research2025

The quantitative impact of 3'UTRs on gene expression.

Jessica D West, Hannah J Smith, Luyen Tien Vu, Elizabeth A Fogarty, Kenneth A Matreyek, Douglas M Fowler, Andrew Grimson

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
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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

7 authors.

Jessica D WestDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.ORCID 0000-0002-5497-0518
Hannah J SmithDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.ORCID 0000-0001-6296-3599
Luyen Tien VuDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.ORCID 0000-0002-4953-6469
Elizabeth A FogartyDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
Kenneth A MatreyekDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States.ORCID 0000-0001-9149-551X
Douglas M FowlerDepartment of Genome Sciences, University of Washington, Seattle, WA 98115, United States.ORCID 0000-0001-7614-1713
Andrew GrimsonDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.ORCID 0000-0002-5794-6484

Funding

Technology to understand genetic variant effects in contextRM1HG010461 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Bruce Colston Trapnell · 2019 to 2026
$18.9M
Spermatogenic gene regulation and infertilityP50HD104454 · NICHD · CORNELL UNIVERSITY · PI GRENIER, JENNIFER K · 2021 to 2025
$8.1M
New approaches for investigating the causes and consequences of cellular heterogeneityR35GM152106 · NIGMS · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler · 2024 to 2026
$1.8M
Establishing Methods to Delineate 3'UTR-mediated RegulationR21HG011512 · NHGRI · CORNELL UNIVERSITY · PI GRIMSON, ANDREW W · 2021 to 2022
$433k
Center for Vertebrate GenomicsNHGRI NIH HHS RM1 HG010461NIH HHS P50HD104454NIH HHS R21HG011512NIH HHS R35GM152106NIH HHS RM1HG010461
6 · The paper itself

Abstract

Control of gene expression is fundamental to biology, and post-transcriptional regulation is an important component of this process. In mammals, the 3'UTR in particular serves as a major source of regulatory information within the transcript. Here we developed an accurate massively parallel reporter assay (MPRA) system to evaluate the impact of >1400 full-length human 3'UTRs on RNA abundance, stability, translational regulation, and total protein output. We demonstrated that our MPRA is consistent with regulation of the corresponding endogenous transcripts. We used the MPRA datasets to model the relative contributions of RNA abundance and translational efficiency toward total 3'UTR-mediated regulation, revealing an unexpectedly large role for 3'UTR-specified translational control, and providing additional evidence that much of 3'UTR-encoded regulation is mediated by concerted regulation of translation plus decay. We observed relationships between GC content and 3'UTR length and different modes of regulation, and identified sequence motifs corresponding to regulatory RNA-binding proteins associated with mediating 3'UTR-dependent gene expression. We compared regulation from >1400 3'UTRs under control of two dissimilar promoters, which revealed promoter-associated differences in post-transcriptional regulation for certain 3'UTRs. Together, this dataset represents a comprehensive characterization of 3'UTR-mediated quantitative regulation.

Indexed as

3' Untranslated RegionsGene Expression RegulationProtein BiosynthesisBase CompositionGenes, ReporterHumansPromoter Regions, GeneticRNA-Binding ProteinsRNA, MessengerRNA Stability3' Untranslated RegionsRNA-Binding ProteinsRNA, Messenger

Identifiers

PMID40586305
PMCPMC12207410

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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.