GENOMIC ANALYSIS OF CLUSTER FX-MIR: POSSIBLE IMPLICATIONS IN FRAGILE X-ASSOCIATED DISORDERS

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

Congreso; Reunión Conjunta SAIC SAI AAFE NANOMEDar; 2021

The Fragile X Mental Retardation-1 (FMR1) gene consists of 17 exons spanning 38 kb of the Xq27.3 chromosome and codes for the protein fragile X mental retardation protein (FMRP). FMR1 is involved, by different molecular mechanisms, in 3 genetic disorders. The absence of FMRP due to an expansion of > 200 CGG repeats in the 5′UTR of the gene (full mutation), is responsible for the Fragile X syndrome (FXS) while the premutation state is associated with the Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI).Recently, a microRNA (miRNA) cluster adjacent to FMR1 (Fx-mir) has been described in placental mammals and it has been shown that a number of miRNAs in the cluster target FMR1 in human and mouse, regulating its expression. In this work we described the Fx-mir cluster and the putative targets of its miRNAs in Rattus norvegicus (rat). In particular, we were interested in studying whether some of the Fx- mir miRNAs target Fmr1 in the rat as well.We used public access databases and performed a reciprocal best hit sequence identity analysis using the human Fx-mir miRNAs as bait in order to find orthologous miRNAs in the rat. We found a total of 18 miRNAs located in the Fx-mir cluster in rat and among them, 8 with a conserved seed region and chromosome location between both species.Next, to study putative targets of Fx-mir miRNAs, we searched for miRNAs predicted to target Fmr1 using the gene of interest as input in specialized target finding softwares. We also made the reverse search, finding every possible target for each miRNA of Fx-mir. We found that miR-880 is a possible regulator of Fmr1.Finally, we extended the search to all of the X chromosome genome sequence, finding 8 more candidates predicted to target Fmr1 that might be of interest.