Evidence map›Paper›PMID 22740638›Full record

ArticleRNA (New York, N.Y.)2012

Disease-linked microRNA-21 exhibits drastically reduced mRNA binding and silencing activity in healthy mouse liver.

John R Androsavich, B Nelson Chau, Balkrishen Bhat, Peter S Linsley, Nils G Walter

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

32 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Non-Coding RNAs as New Therapeutic Targets in the Context of Renal Fibrosis.International journal of molecular sciences · 2019
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

5 authors at 2 institutions in 1 country.

John R AndrosavichDepartment of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.
B Nelson Chau
Balkrishen Bhat
Peter S Linsley
Nils G Walter
Regulus Therapeutics (United States) · USUniversity of Michigan · US

Funding

Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
Trekking with the Ribognome: Single Molecule Microscopy of Intracellular miRNPsR01GM081025 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WALTER, NILS G · 2007 to 2010
$998k
NIGMS NIH HHS GM081025NIGMS NIH HHS R01 GM081025NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

MicroRNAs (miRNAs) bind to mRNAs and fine-tune protein output by affecting mRNA stability and/or translation. miR-21 is a ubiquitous, highly abundant, and stress-responsive miRNA linked to several diseases, including cancer, fibrosis, and inflammation. Although the RNA silencing activity of miR-21 in diseased cells has been well documented, the roles of miR-21 under healthy cellular conditions are not well understood. Here, we show that pharmacological inhibition or genetic deletion of miR-21 in healthy mouse liver has little impact on regulation of canonical seed-matched mRNAs and only a limited number of genes enriched in stress response pathways. These surprisingly weak and selective regulatory effects on known and predicted target mRNAs contrast with those of other abundant liver miRNAs such as miR-122 and let-7. Moreover, miR-21 shows greatly reduced binding to polysome-associated target mRNAs compared to miR-122 and let-7. Bioinformatic analysis suggests that reduced thermodynamic stability of seed pairing and target binding may contribute to this deficiency of miR-21. Significantly, these trends are reversed in human cervical carcinoma (HeLa) cells, where miRNAs including miR-21 show enhanced target binding within polysomes and where miR-21 triggers strong degradative activity toward target mRNAs. Taken together, our results suggest that, under normal cellular conditions in liver, miR-21 activity is maintained below a threshold required for binding and silencing most of its targets. Consequently, enhanced association with polysome-associated mRNA is likely to explain in part the gain of miR-21 function often found in diseased or stressed cells.

Indexed as

AnimalsBlotting, WesternGene Expression ProfilingHeLa CellsHumansLiverMaleMiceMice, Inbred C57BLMicroRNAsOligonucleotide Array Sequence AnalysisPolyribosomesProtein BiosynthesisRNA, MessengerRNA StabilityMicroRNAsMIRN21 microRNA, humanMIRN21 microRNA, mouseRNA, Messenger

Identifiers

PMID22740638
PMCPMC3404372
OpenAlexW2135535411

What OpenQuestion holds

Textmetadata
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.