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

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Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9
Title:
Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9
Journal Title:
Nucleic Acids Research
Keywords:
Publication Date:
04 May 2018
Citation:
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, Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9, Nucleic Acids Research, Volume 46, Issue 14, 21 August 2018, Pages 7323–7338, https://doi.org/10.1093/nar/gky348
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.
License type:
http://creativecommons.org/licenses/by-nc/4.0/
Funding Info:
Singapore National Medical Research Council [NMRC/CBRG/0077/2014]; Singapore Ministry of Education [MOE2014-T3-1-006, T1-2015 Apr-03]; K.K. is supported by the Ministry of Education AcRF Tier 3 Programme Seed Funding; G.W.Y. is funded by the National University of Singapore and National Research Foundation of Singapore. Funding for open access charge: Research grant. Conflict of interest statement. None declared.
Description:
ISSN:
1362-4962
0305-1048
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