PT  - JOURNAL ARTICLE
AU  - Joshua A. Chu-Tan
AU  - Zhi-Ping Feng
AU  - Yvette Wooff
AU  - Adrian V. Cioanca
AU  - Ulrike Schumann
AU  - Riemke Aggio-Bruce
AU  - Hardip Patel
AU  - Matt Rutar
AU  - Katherine Hannan
AU  - Konstantin Panov
AU  - Jan Provis
AU  - Riccardo Natoli
TI  - Functional microRNA targetome undergoes degeneration-induced shift in the retina
AID  - 10.1101/2020.05.27.118307
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.27.118307
4099  - http://biorxiv.org/content/early/2020/05/27/2020.05.27.118307.short
4100  - http://biorxiv.org/content/early/2020/05/27/2020.05.27.118307.full
AB  - 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 StatementThe authors have declared no competing interest.