Evidence mapPaperPMID 38197221Full record

ArticleNucleic acids research2024

Discovery of novel microRNA mimic repressors of ribosome biogenesis.

Carson J Bryant, Mason A McCool, Gabriela T Rosado González, Laura Abriola, Yulia V Surovtseva, Susan J Baserga

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Carson J BryantDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, 06520, USA.ORCID 0000-0002-7475-875X
Mason A McCoolDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, 06520, USA.ORCID 0000-0001-7834-0927
Gabriela T Rosado GonzálezDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, 06520, USA.
Laura AbriolaYale Center for Molecular Discovery, Yale University, West Haven, CT, 06516, USA.ORCID 0000-0002-7304-6531
Yulia V SurovtsevaYale Center for Molecular Discovery, Yale University, West Haven, CT, 06516, USA.ORCID 0000-0001-6079-9246
Susan J BasergaDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, 06520, USA.ORCID 0000-0002-7731-8629
Yale University · US

Funding

PREDOCTORAL PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYT32GM007223 · YALE UNIVERSITY · 1985 to 2005
$9.4M
Novel regulatory networks driving human ribosome biogenesisR35GM131687 · NIGMS · YALE UNIVERSITY · 2024 to 2025
$1.4M
NIDCR NIH HHS F31 DE030332NIGMS NIH HHS R35 GM131687NIGMS NIH HHS T32 GM007223NIH HHS 1R35GM131687NIH HHS S10 OD030363
6 · The paper itself

Abstract

While microRNAs and other non-coding RNAs are the next frontier of novel regulators of mammalian ribosome biogenesis (RB), a systematic exploration of microRNA-mediated RB regulation has not yet been undertaken. We carried out a high-content screen in MCF10A cells for changes in nucleolar number using a library of 2603 mature human microRNA mimics. Following a secondary screen for nucleolar rRNA biogenesis inhibition, we identified 72 novel microRNA negative regulators of RB after stringent hit calling. Hits included 27 well-conserved microRNAs present in MirGeneDB, and were enriched for mRNA targets encoding proteins with nucleolar localization or functions in cell cycle regulation. Rigorous selection and validation of a subset of 15 microRNA hits unexpectedly revealed that most of them caused dysregulated pre-rRNA processing, elucidating a novel role for microRNAs in RB regulation. Almost all hits impaired global protein synthesis and upregulated CDKN1A (p21) levels, while causing diverse effects on RNA Polymerase 1 (RNAP1) transcription and TP53 protein levels. We provide evidence that the MIR-28 siblings, hsa-miR-28-5p and hsa-miR-708-5p, potently target the ribosomal protein mRNA RPS28 via tandem primate-specific 3' UTR binding sites, causing a severe pre-18S pre-rRNA processing defect. Our work illuminates novel microRNA attenuators of RB, forging a promising new path for microRNA mimic chemotherapeutics.

Indexed as

MicroRNAsRibosomesRNA PrecursorsAnimalsHumansMammalsRNA, MessengerTranscription FactorsMicroRNAsRNA, MessengerRNA PrecursorsTranscription Factors

Identifiers

PMID38197221
PMCPMC10899765
OpenAlexW4390701313

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.