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  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., 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.

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 Creators:
Huang, H., Author
Kapeli, K., Author
Jin, W., Author
Wong, Y. P., Author
Arumugam, T. V., Author
Koh, J. H., Author
Srimasorn, S., Author
Mallilankaraman, K., Author
Chua, J. J. E.1, Author           
Yeo, G. W., Author
Soong, T. W., Author
Affiliations:
1Research Group of Protein Trafficking in Synaptic Development and Function, MPI for Biophysical Chemistry, Max Planck Society, ou_1933287              

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 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.

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Language(s): eng - English
 Dates: 2018-05-042018-08-21
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1093/nar/gky348
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Title: Nucleic Acids Research
Source Genre: Journal
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Pages: - Volume / Issue: 46 (14) Sequence Number: - Start / End Page: 7323 - 7338 Identifier: -