Evidence map›Paper›PMID 35033060›Full record

ArticleMolecular cancer2022

A nuclear function for an oncogenic microRNA as a modulator of snRNA and splicing.

Rachid El Fatimy, Yanhong Zhang, Evgeny Deforzh, Mahalakshmi Ramadas, Harini Saravanan, Zhiyun Wei, Rosalia Rabinovsky, Nadiya M Teplyuk, Erik J Uhlmann, Anna M Krichevsky

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

25 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review
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

10 authors at 1 institution in 3 countries.

Rachid El Fatimy *Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Yanhong Zhang *Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Evgeny DeforzhDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Mahalakshmi RamadasDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Harini SaravananDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Zhiyun WeiDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Rosalia RabinovskyDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Nadiya M TeplyukDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Erik J UhlmannDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA.
Anna M KrichevskyDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Room 9002T, Boston, MA, 02115, USA. akrichevsky@bwh.harvard.edu.ORCID 0000-0002-5080-5507
Brigham and Women's Hospital · US

Funding

Epigenetics and 3D Structure of miR-10b/HoxD Locus in the Brain and Malignant GliomaR01NS113929 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KRICHEVSKY, ANNA M. · 2020 to 2024
$3.1M
Developing miR-10b targeting for glioblastomaR01CA215072 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KRICHEVSKY, ANNA M. · 2018 to 2022
$2.0M
Deciphering regulatory RNA networks underlying molecular pathology in Alzheimer's diseaseR21AG060019 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI KRICHEVSKY, ANNA M. · 2018 to 2019
$492k
National Foundation for Cancer Research R01CA215072NCI NIH HHS R01 CA215072NIA NIH HHS R21 AG060019NIA NIH HHS R21AG060019NINDS NIH HHS R01 NS113929NINDS NIH HHS R01NS113929
6 · The paper itself

Abstract

backgroundmiRNAs are regulatory transcripts established as repressors of mRNA stability and translation that have been functionally implicated in carcinogenesis. miR-10b is one of the key onco-miRs associated with multiple forms of cancer. Malignant gliomas exhibit particularly striking dependence on miR-10b. However, despite the therapeutic potential of miR-10b targeting, this miRNA's poorly investigated and largely unconventional properties hamper the clinical translation.

methodsWe utilized Covalent Ligation of Endogenous Argonaute-bound RNAs and their high-throughput RNA sequencing to identify miR-10b interactome and a combination of biochemical and imaging approaches for target validation. They included Crosslinking and RNA immunoprecipitation with spliceosomal proteins, a combination of miRNA FISH with protein immunofluorescence in glioma cells and patient-derived tumors, native Northern blotting, and the transcriptome-wide analysis of alternative splicing.

resultsWe demonstrate that miR-10b binds to U6 snRNA, a core component of the spliceosomal machinery. We provide evidence of the direct binding between miR-10b and U6, in situ imaging of miR-10b and U6 co-localization in glioma cells and tumors, and biochemical co-isolation of miR-10b with the components of the spliceosome. We further demonstrate that miR-10b modulates U6 N-6-adenosine methylation and pseudouridylation, U6 binding to splicing factors SART3 and PRPF8, and regulates U6 stability, conformation, and levels. These effects on U6 result in global splicing alterations, exemplified by the altered ratio of the isoforms of a small GTPase CDC42, reduced overall CDC42 levels, and downstream CDC42 -mediated effects on cell viability.

conclusionsWe identified U6 snRNA, the key RNA component of the spliceosome, as the top miR-10b target in glioblastoma. We, therefore, present an unexpected intersection of the miRNA and splicing machineries and a new nuclear function for a major cancer-associated miRNA.

Indexed as

Gene Expression Regulation, NeoplasticOncogenesRNA SplicingAlternative SplicingAntigens, Neoplasmcdc42 GTP-Binding ProteinCell Line, TumorCell NucleusHumansMembrane GlycoproteinsMicroRNAsModels, BiologicalReceptors, ImmunologicRNA-Binding ProteinsRNA InterferenceRNA, Small NuclearAntigens, Neoplasmcdc42 GTP-Binding ProteinLILRB2 protein, humanMembrane GlycoproteinsMicroRNAsPRPF8 protein, humanReceptors, ImmunologicRNA-Binding ProteinsRNA, Small NuclearSART3 protein, humanU6 small nuclear RNACDC42GlioblastomamiR-10bNucleusSplicing machineryU6 snRNA

Identifiers

PMID35033060
PMCPMC8760648
OpenAlexW4225255070

What OpenQuestion 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 OpenQuestion graph.