Alternative splicing (AS) plays a critical role in enhancing proteome complexity in higher eukaryotes. Almost all the multi intron-containing genes undergo AS in humans. Splicing mainly occurs co-transcriptionally, where RNA polymerase II (RNA pol II) plays a crucial role in coordinating transcription and pre-mRNA splicing. Aberrant AS leads to non-functional proteins causative in various pathophysiological conditions such as cancers, neurodegenerative diseases, and muscular dystrophies. Transcription and pre-mRNA splicing are deeply interconnected and can influence each other's functions. Several studies evinced that specific promoters employed by RNA pol II dictate the RNA processing decisions. Promoter-specific recruitment of certain transcriptional factors or transcriptional coactivators influences splicing, and the extent to which these factors affect splicing has not been discussed in detail. Here, in this review, various DNA-binding proteins and their influence on promoter-specific AS are extensively discussed. Besides, this review highlights how the promoter-specific epigenetic changes might regulate AS.
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