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Functional microRNA targetome undergoes degeneration-induced shift in the retina.
Chu-Tan, Joshua A; Cioanca, Adrian V; Feng, Zhi-Ping; Wooff, Yvette; Schumann, Ulrike; Aggio-Bruce, Riemke; Patel, Hardip; Rutar, Matt; Hannan, Katherine; Panov, Konstantin; Provis, Jan; Natoli, Riccardo.
Afiliación
  • Chu-Tan JA; 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.
  • Cioanca AV; The Australian National University Medical School, College of Health and Medicine, Canberra, ACT, 2601, Australia.
  • Feng ZP; 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.
  • Wooff Y; The ANU Bioinformatics Consultancy, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
  • Schumann U; 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.
  • Aggio-Bruce R; The Australian National University Medical School, College of Health and Medicine, Canberra, ACT, 2601, Australia.
  • Patel H; 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.
  • Rutar M; 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.
  • Hannan K; The Australian National University Medical School, College of Health and Medicine, Canberra, ACT, 2601, Australia.
  • Panov K; The ANU Bioinformatics Consultancy, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, Canberra, ACT, 2601, Australia.
  • Provis J; School of Biomedical Sciences, The University of Melbourne, Parkville, Victoria, 3010, Australia.
  • Natoli R; Faculty of Science and Technology, University of Canberra, Bruce, ACT, 2617, Australia.
Mol Neurodegener ; 16(1): 60, 2021 08 31.
Article en En | MEDLINE | ID: mdl-34465369
ABSTRACT

BACKGROUND:

MicroRNA (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.

METHODS:

To 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).

RESULTS:

Analysis 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.

CONCLUSIONS:

This 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / MicroARNs / Proteínas del Ojo / Degeneración Macular Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Neurodegener Año: 2021 Tipo del documento: Article País de afiliación: Australia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / MicroARNs / Proteínas del Ojo / Degeneración Macular Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Neurodegener Año: 2021 Tipo del documento: Article País de afiliación: Australia