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Functional microRNA targetome undergoes degeneration-induced shift in the retina

View ORCID ProfileJoshua A. Chu-Tan, Zhi-Ping Feng, Yvette Wooff, Adrian V. Cioanca, Ulrike Schumann, Riemke Aggio-Bruce, Hardip Patel, Matt Rutar, Katherine Hannan, Konstantin Panov, Jan Provis, Riccardo Natoli
doi: https://doi.org/10.1101/2020.05.27.118307
Joshua A. Chu-Tan
1Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
2The Australian National University Medical School, College of Health and Medicine, Acton, ACT 2601, Australia
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  • ORCID record for Joshua A. Chu-Tan
Zhi-Ping Feng
3The ANU Bioinformatics Consultancy, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
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Yvette Wooff
1Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
2The Australian National University Medical School, College of Health and Medicine, Acton, ACT 2601, Australia
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Adrian V. Cioanca
1Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
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Ulrike Schumann
1Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
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Riemke Aggio-Bruce
1Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
2The Australian National University Medical School, College of Health and Medicine, Acton, ACT 2601, Australia
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Hardip Patel
3The ANU Bioinformatics Consultancy, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
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Matt Rutar
4School of Biomedical Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia
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Katherine Hannan
5ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
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Konstantin Panov
6School of Biological Sciences, Queen’s University Belfast, Belfast BT9 5DL, Northern Ireland
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Jan Provis
1Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
2The Australian National University Medical School, College of Health and Medicine, Acton, ACT 2601, Australia
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Riccardo Natoli
1Eccles Institute of Neuroscience, The John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT 2601, Australia
2The Australian National University Medical School, College of Health and Medicine, Acton, ACT 2601, Australia
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  • For correspondence: riccardo.natoli@anu.edu.au
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Summary

MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases, including age-related macular degeneration, acting as post-transcriptional gene suppressors through their association with argonaute (AGO) protein family members. However, to understand their role in disease, investigation into the regulatory nature of miRNA with their targets is required. To identify the active-miRnome-targetome interactions in the degenerating retina, AGO2 HITS-CLIP was performed using a mouse model of retinal degeneration. Analysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed. This shift was also demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal miRNA loaded in AGO2. Following damage, AGO2 was localised to the inner retinal layers indicating a locational miRNA response to retinal damage. This study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 27, 2020.
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Functional microRNA targetome undergoes degeneration-induced shift in the retina
Joshua A. Chu-Tan, Zhi-Ping Feng, Yvette Wooff, Adrian V. Cioanca, Ulrike Schumann, Riemke Aggio-Bruce, Hardip Patel, Matt Rutar, Katherine Hannan, Konstantin Panov, Jan Provis, Riccardo Natoli
bioRxiv 2020.05.27.118307; doi: https://doi.org/10.1101/2020.05.27.118307
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Functional microRNA targetome undergoes degeneration-induced shift in the retina
Joshua A. Chu-Tan, Zhi-Ping Feng, Yvette Wooff, Adrian V. Cioanca, Ulrike Schumann, Riemke Aggio-Bruce, Hardip Patel, Matt Rutar, Katherine Hannan, Konstantin Panov, Jan Provis, Riccardo Natoli
bioRxiv 2020.05.27.118307; doi: https://doi.org/10.1101/2020.05.27.118307

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