Evidence map›Paper›PMID 38273160›Full record

ArticleMolecular systems biology2024

A ubiquitous GC content signature underlies multimodal mRNA regulation by DDX3X.

Ziad Jowhar, Albert Xu, Srivats Venkataramanan, Francesco Dossena, Mariah L Hoye, Debra L Silver, Stephen N Floor, Lorenzo Calviello

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 3 countries.

Ziad Jowhar *Department of Cell and Tissue Biology, UCSF, San Francisco, USA.ORCID http://orcid.org/0000-0002-3536-079X
Albert Xu *Department of Cell and Tissue Biology, UCSF, San Francisco, USA.ORCID http://orcid.org/0000-0001-5938-561X
Srivats VenkataramananDepartment of Cell and Tissue Biology, UCSF, San Francisco, USA.ORCID http://orcid.org/0000-0002-2507-401X
Francesco DossenaHuman Technopole, Milan, Italy.ORCID http://orcid.org/0009-0005-4948-4805
Mariah L HoyeDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, USA.ORCID http://orcid.org/0000-0002-3430-2782
Debra L SilverDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, USA.ORCID http://orcid.org/0000-0001-9189-844X
Stephen N FloorDepartment of Cell and Tissue Biology, UCSF, San Francisco, USA. Stephen.Floor@ucsf.edu.ORCID http://orcid.org/0000-0002-9965-9694
Lorenzo CalvielloHuman Technopole, Milan, Italy. Lorenzo.Calviello@fht.org.ORCID http://orcid.org/0000-0002-5600-0988
Duke University · USHuman Technopole · ITUniversity of California, San Francisco · USCell and Tissue Systems (United States) · USUniversity of Cienfuegos · CU

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Medical Scientist Training Program (T32 NRSA Training Grant)T32GM141323 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aimee Kao · 2021 to 2026
$10.5M
Investigating sex differences in DDX3X mouse modelsR01NS120667 · NINDS · DUKE UNIVERSITY · PI SILVER, DEBRA L. · 2021 to 2025
$3.4M
The impact of human RNA diversity on protein production and cell fateDP2GM132932 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FLOOR, STEPHEN NICHOLAS · 2018 to 2018
$2.4M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
Investigating the role of DDX3 in regulating RNA structure and mRNA exportF30HD110250 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI XU, ALBERT Y · 2022 to 2025
$187k
NICHD NIH HHS F30 HD110250NIGMS NIH HHS DP2 GM132932NIGMS NIH HHS T32 GM007618NIGMS NIH HHS T32 GM141323NIH HHS S10 OD028511NINDS NIH HHS R01 NS120667
6 · The paper itself

Abstract

The road from transcription to protein synthesis is paved with many obstacles, allowing for several modes of post-transcriptional regulation of gene expression. A fundamental player in mRNA biology is DDX3X, an RNA binding protein that canonically regulates mRNA translation. By monitoring dynamics of mRNA abundance and translation following DDX3X depletion, we observe stabilization of translationally suppressed mRNAs. We use interpretable statistical learning models to uncover GC content in the coding sequence as the major feature underlying RNA stabilization. This result corroborates GC content-related mRNA regulation detectable in other studies, including hundreds of ENCODE datasets and recent work focusing on mRNA dynamics in the cell cycle. We provide further evidence for mRNA stabilization by detailed analysis of RNA-seq profiles in hundreds of samples, including a Ddx3x conditional knockout mouse model exhibiting cell cycle and neurogenesis defects. Our study identifies a ubiquitous feature underlying mRNA regulation and highlights the importance of quantifying multiple steps of the gene expression cascade, where RNA abundance and protein production are often uncoupled.

Indexed as

Gene Expression RegulationRNAAnimalsBase CompositionCell CycleMiceRNA, MessengerRNARNA, MessengerComputational BiologyDDX3XmRNA BiologyTranscriptomicsTranslation

Identifiers

PMID38273160
PMCPMC10912769
OpenAlexW4391223542

What Socratic holds

Textmetadata
LicenceCC BY
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.