Alternative splicing is controlled by cis-regulatory sequences present in the pre-mRNA and their cognate trans-acting factors, as well as by its coupling to RNA polymerase II (pol II) transcription. A unique feature of this polymerase is the presence of a highly repetitive carboxy terminal domain (CTD), which is subject to multiple regulatory post-translational modifications. CTD phosphorylation events affect the transcriptional properties of pol II and the outcome of co-transcriptional alternative splicing by mediating the effects of splicing factors and by modulating transcription elongation rates. Here, we discuss various examples of involvement of the CTD in alternative splicing regulation as well as the current methodological limitations in deciphering the detailed mechanisms of this process.
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