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

Huang, H.; Kapeli, K.; Jin, W.; Wong, Y. P.; Arumugam, T. V.; Koh, J. H.; Srimasorn, S.; Mallilankaraman, K.; Chua, J. J. E.; Yeo, G. W.; Soong, T. W.

doi:10.1093/nar/gky348

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

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Chua, J. J. E.
Research Group of Protein Trafficking in Synaptic Development and Function, MPI for Biophysical Chemistry, Max Planck Society;

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Citation

Huang, H., Kapeli, K., Jin, W., Wong, Y. P., Arumugam, T. V., Koh, J. H., et al. (2018). Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9. Nucleic Acids Research, 46(14), 7323-7338. doi:10.1093/nar/gky348.

Cite as: https://hdl.handle.net/21.11116/0000-0001-F46D-2

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.