期刊
RNA
卷 13, 期 7, 页码 1071-1078出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.404407
关键词
RNA editing; ADAR; RNA polymerase II; CTD; RNA processing
资金
- NIGMS NIH HHS [R01 GM058613, GM58613] Funding Source: Medline
The C-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II) influences many steps in the synthesis of an mRNA and helps control the final destiny of the mature transcript. ADAR2 edits RNA by converting adenosine to inosine within double- stranded or structured RNA. Site- selective A-to-I editing often occurs at sites near exon/ intron borders, where it depends on intronic sequences for substrate recognition. It is therefore essential that editing precedes splicing. We have investigated whether there is coordination between ADAR2 editing and splicing of the GluR-B pre-mRNA. We show that the CTD is required for efficient editing at the R/ G site one base upstream of a 5'-splice site. The results suggest that the CTD enhances editing at the R/ G site by preventing premature splicing that would remove the intronic recognition sites for ADAR2. Editing at the GluR-B Q/ R site, 24 bases upstream of the intron 11 5'-splice site, stimulates splicing at this intron. Furthermore, unlike previously studied introns, the CTD actually inhibits excision of intron 11, which includes the complementary recognition sequences for the Q/ R editing site. In summary, these results show that the CTD and ADAR2 function together to enforce the order of events that allows editing to precede splicing, and they furthermore suggest a new role for the CTD as a coordinator of two interdependent pre-mRNA processing events.
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