Evidence map›Paper›PMID 34465369›Full record

ArticleMolecular neurodegeneration2021

Functional microRNA targetome undergoes degeneration-induced shift in the retina.

Joshua A Chu-Tan, Adrian V Cioanca, Zhi-Ping Feng, Yvette Wooff, Ulrike Schumann, Riemke Aggio-Bruce, Hardip Patel, Matt Rutar, Katherine Hannan, Konstantin Panov and 2 more

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

Article in Molecular neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Small Differences and Big Changes: The Many Variables of MicroRNA Expression and Function in the Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Serum miRNA modulations indicate changes in retinal morphology.Frontiers in molecular neuroscience · 2023
    Article
  12. Article
  13. Review
  14. 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

12 authors at 3 institutions in 2 countries.

Joshua A Chu-Tan *Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Adrian V Cioanca *Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Zhi-Ping FengThe ANU Bioinformatics Consultancy, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Yvette WooffEccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Ulrike SchumannEccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Riemke Aggio-BruceEccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Hardip PatelThe ANU Bioinformatics Consultancy, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Matt RutarSchool of Biomedical Sciences, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Katherine HannanACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Konstantin PanovSchool of Biological Sciences Queen's University Belfast, Belfast, BT9 5DL, Northern Ireland.
Jan ProvisEccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
Riccardo NatoliEccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia. riccardo.natoli@anu.edu.au.ORCID 0000-0002-9350-0439
Australian National University · AUQueen's University Belfast · GBThe University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC). Identifying the retinal miRNA/mRNA interactions in health and disease will provide important insight into the key pathways miRNA regulate in disease pathogenesis and may lead to potential therapeutic targets to mediate retinal degeneration.

methodsTo identify the active miRnome targetome interactions in the healthy and degenerating retina, AGO2 HITS-CLIP was performed using a rodent model of photoreceptor degeneration. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data was performed to identify the cellular location of AGO2 and key members of the microRNA targetome in the retina. AGO2 findings were verified by in situ hybridization (RNA) and immunohistochemistry (protein).

resultsAnalysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed with an enrichment of miRNA involvement in inflammatory pathways. This shift was further demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal AGO2-bound miRNA, and has known roles in regulating retinal inflammation. Additionally, photoreceptor cluster miR-183/96/182 were all among the most highly abundant miRNA bound to AGO2. Following damage, AGO2 expression was localized to the inner retinal layers and more in the OLM than in healthy retinas, indicating a locational miRNA response to retinal damage.

conclusionsThis study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration and explores the miRNA-mRNA targetome as a consequence of retinal degenerations. Further characterisation of these miRNA/mRNA interactions in the context of the degenerating retina may provide an important insight into the active role these miRNA may play in diseases such as AMD.

Indexed as

AnimalsArgonaute ProteinsDisease Models, AnimalEye ProteinsHigh-Throughput Nucleotide SequencingHumansImmunoprecipitationInflammationLightMacular DegenerationMiceMice, Inbred C57BLMice, TransgenicMicroRNAsOxidative StressRetinaAgo2 protein, mouseArgonaute ProteinsEye ProteinsMicroRNAsRNA-Induced Silencing ComplexArgonauteHITS-CLIPInflammationmicroRNAmRNARetinaRetinal degenerationTranscriptome

Identifiers

PMID34465369
PMCPMC8406976
OpenAlexW3196580914

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.