Title: Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9.

Authors: Hua Huang, Katannya Kapeli, Wenhao Jin, Yuk Peng Wong, Thiruma Valavan Arumugam, Joanne Huifen Koh, Sumitra Srimasorn, Karthik Mallilankaraman, John Jia En Chua, Gene W Yeo, Tuck Wah Soong

Journal, date & volume: Nucleic Acids Res, 2018Aug21, 46, 7323-7338

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/29733375

Abstract
Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of voltage-gated calcium channel CaV1.3 are subject to brain-selective A-to-I RNA editing by ADAR2. Here, we show that editing of CaV1.3 mRNA is dependent on a 40 bp RNA duplex formed between exon 41 and an evolutionarily conserved editing site complementary sequence (ECS) located within the preceding intron. Heterologous expression of a mouse minigene that contained the ECS, intermediate intronic sequence and exon 41 with ADAR2 yielded robust editing. Interestingly, editing of CaV1.3 was potently inhibited by serine/arginine-rich splicing factor 9 (SRSF9). Mechanistically, the inhibitory effect of SRSF9 required direct RNA interaction. Selective down-regulation of SRSF9 in neurons provides a basis for the neuron-specific editing of CaV1.3 transcripts.