In silico analysis of the expression levels of microRNAs predicted to target Fmr1: possible implications in Fragile X-Associated Diseases

MARINA LUZ INGRAVIDI; IANINA FERDER; LILIANA DAIN; LAURA KAMENETZKY

Congreso; Congreso Argentino de Bioinformática y Biología Computacional; 2022

BACKGROUNDThe Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene is located on the X chromosome and codes for the Synaptic Functional Regulator FMR1 Protein (FMRP). This gene is involved, by different molecular mechanisms, in 3 genetic disorders. Our group is interested in Fragile X Associated Primary Ovarian Insufficiency (FXPOI), a disorder that causes early menopause and sub-fertility/infertility, among others.Many studies show a correlation between the dysregulation of some microRNAs and the FMR1 transcript levels in different cell types of patients with Fragile X-associated diseases. Moreover, a microRNA cluster adjacent to Fmr1, Fx-mir, was recently described in mammals. Some of these microRNAs were shown to target FMR1 in mouse and human tissues.Our aim is to understand the regulation of Fmr1 by microRNAs in a model of follicular development in rat.In this work, we extended our previous research on the rat’s Fmr1 regulators located in Fx-mir. To do so, we predicted all potential microRNAs that target Fmr1 and performed in silico analysis of the expression levels of microRNAs in the rat ovary. RESULTSUsing three specialized microRNA-target finding softwares (MIRANDA, DIANA, miRDB) we found 65 microRNAs predicted to target Fmr1. Five out of the top 30 were identified by the three softwares and 22 with at least two of them.We then searched for microRNA expression in the rat’s ovary by analyzing publicly available small RNA-seq studies. We found 356 microRNAs expressed in the ovary.Within the forementioned 22 microRNAs that have Fmr1 as a potential target, 3 belong to the high group, 8 to the middle group, and 12 to the low group.CONCLUSIONSEven though most of the microRNAs predicted to target Fmr1 show a middle/low expression in the ovary, we found 3 microRNAs with a high predicted target score (rno-miR-148a-3p, rno-miR-92a-3p and rno-miR-19b-3p), that makes them good candidates to regulate Fmr1 in our model. We will experimentally validate these findings in our model of follicular development to understand their potential role in FXPOI.