TNF-alpha regulates alternative splicing of genes participating in pathways of crucial metabolic syndromes; a transcriptome wide study

Global analysis of RNA–protein interactions in TNF‐α induced alternative splicing in metabolic disorders

“…4D, Appendix S10), involvement of both the genes in metabolic disorders has been reported previously [33,34]. We have already validated and reported the modulation of AS of CREB5 by TNF-a [22]. The next most frequently occurring RPI is RBMX-CCAG (occurs 183 times, Appendix S9), and the high frequency of this interaction has also been Fig.…”

“…Our published RNA-seq data, used as the basis for this study, categorized the splicing events into the four major classes: CE, A5 0 , A3 0 , and MEE. According to our previous study, out of a total of 8417 statistically significant AS events, CE, A5 0 , A3 0 , and MEE corresponded to 4155, 1990, 2250, and 22 events, respectively [22]. The RNA sequence used as the input to the RBPDB database [24] includes the sequences encompassing the splicing event start and end as well as 50 nucleotides both up and downstream of the spliced RNA (see Materials and methods) (Appendix S1).…”

“…We shortlisted 228 genes, which were significantly regulated at the AS level among the total gene pool. Out of which, 56 genes contributed toward various metabolic syndromes including T2DM, obesity, and insulin resistance [22]. In this study, we have performed bioinformatics analysis using RBPDB to elucidate the correlation between the RNA motifs of these genes and the RBPs that are involved.…”

“…Our published RNA‐seq data, used as the basis for this study, categorized the splicing events into the four major classes: CE, A5′, A3′, and MEE. According to our previous study, out of a total of 8417 statistically significant AS events, CE, A5′, A3′, and MEE corresponded to 4155, 1990, 2250, and 22 events, respectively [22].…”

“…This further elevates free fatty acid levels in blood and impairs insulin signaling pathways leading to various metabolic disorders [21]. Out of the 228 genes identified, 56 genes were revealed to be involved in various metabolic syndromes including T2DM, obesity, and insulin resistance [22]. In the current study, we have performed a bioinformatics analysis and found unique RBP–RNA interactions in all the four classes of AS with four‐mer sequences as the most frequently occurring RBP binding RNA motifs.…”