RNA editing and alternative splicing: the importance of co‐transcriptional coordination

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Abstract
The carboxy‐terminal domain (CTD) of the large subunit of RNA polymerase II (pol II) is essential for several co‐transcriptional pre‐messenger RNA processing events, including capping, 3′‐end processing and splicing. We investigated the role of the CTD of RNA pol II in the coordination of A to I editing and splicing of the ADAR2 (ADAR: adenosine deaminases that act on RNA) pre‐mRNA. The auto‐editing of Adar2 intron 4 by the ADAR2 adenosine deaminase is tightly coupled to splicing, as the modification of the dinucleotide AA to AI creates a new 3′ splice site. Unlike other introns, the CTD is not required for efficient splicing of intron 4 at either the normal 3′ splice site or the alternative site created by editing. However, the CTD is required for efficient co‐transcriptional auto‐editing of ADAR2 intron 4. Our results implicate the CTD in site‐selective RNA editing by ADAR2 and in coordination of editing with alternative splicing.