RT Journal Article SR Electronic T1 Functional microRNA targetome undergoes degeneration-induced shift in the retina JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.27.118307 DO 10.1101/2020.05.27.118307 A1 Joshua A. Chu-Tan A1 Zhi-Ping Feng A1 Yvette Wooff A1 Adrian V. Cioanca A1 Ulrike Schumann A1 Riemke Aggio-Bruce A1 Hardip Patel A1 Matt Rutar A1 Katherine Hannan A1 Konstantin Panov A1 Jan Provis A1 Riccardo Natoli YR 2020 UL http://biorxiv.org/content/early/2020/05/27/2020.05.27.118307.abstract 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.