Polyadenylation is a process in which a precursor mRNA (pre-mRNA) is cleaved, followed by the addition of a polyadenine tail (poly-A tail). The polyadenylation site (PA site) is marked by the polyadenylation signal (PA signal) and other cis-elements. Alternative polyadenylation (APA) is a post-transcriptional regulatory mechanism that generates multiple mRNA isoforms from one gene by varying the location of polyadenylation sites within the transcript. It is linked with different diseases, including obesity. In this study, we examined genetic variants in the PA signals in obesity-related genes. The examination was performed in mouse lines selected for fatness and leanness. Obesity-related genes (495) were obtained from the IMPC database, and PA sites were obtained from the PolyASite 2.0 database. Genetic variants were available by prior sequencing of the genome of selected lines, which were created by crossing the inbred lines JU and CBA and the outbred line CFLP. After filtering of genetic variants using the RStudio software tool, we found out that 61 PA signals in 56 genes were altered due to the variants. Among these, we highlighted genes in which genetic variants caused: 1. loss/gain of canonic signal (AATAAA or ATTAAA), 2. loss of the only signal in the sequence, or 3. a creation of a completely new signal while the reference genome had no other signals. These genes include Cep250, Tnik for fat line and Alg8, Arhgef4, Cnot4, Csmd3, Dscc1, Gxylt2, Usp15 for lean line. In future research, it would be necessary to investigate the functional impact of variants within the PA signals, to check whether the variants have an impact on APA, and to examine the conservation of genetic polymorphisms in the PA signal between different lines of mice and other species.
|
