RNA editing and alternative splicing: the importance of co-transcriptional coordination.
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.
Laurencikiene
Jurga
J
Department of Molecular Biology and Functional Genomics, Stockholm University, 106 91 Stockholm, Sweden.
Källman
Annika M
AM
Fong
Nova
N
Bentley
David L
DL
Ohman
Marie
M
D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing; D012319:RNA Polymerase II / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D014158:Transcription, Genetic
D016601:RNA-Binding Proteins; D012313:RNA; D012319:RNA Polymerase II; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase