| First Author | Wu D | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 52 | Pages | 18199-18212 |
| PubMed ID | 33100268 | Mgi Jnum | J:300916 |
| Mgi Id | MGI:6490896 | Doi | 10.1074/jbc.RA120.016049 |
| Citation | Wu D, et al. (2020) Distant coupling between RNA editing and alternative splicing of the osmosensitive cation channel Tmem63b. J Biol Chem 295(52):18199-18212 |
| abstractText | Post-transcriptional modifications of pre-mRNAs expand the diversity of proteomes in higher eukaryotes. In the brain, these modifications diversify the functional output of many critical neuronal signal molecules. In this study, we identified a brain-specific A-to-I RNA editing that changed glutamine to arginine (Q/R) at exon 20 and an alternative splicing of exon 4 in Tmem63b, which encodes a ubiquitously expressed osmosensitive cation channel. The channel isoforms lacking exon 4 occurred in approximately 80% of Tmem63b mRNAs in the brain but were not detected in other tissues, suggesting a brain-specific splicing. We found that the Q/R editing was catalyzed by Adar2 (Adarb1) and required an editing site complementary sequence located in the proximal 5' end of intron 20. Moreover, the Q/R editing was almost exclusively identified in the splicing isoform lacking exon 4, indicating a coupling between the editing and the splicing. Elimination of the Q/R editing in brain-specific Adar2 knockout mice did not affect the splicing efficiency of exon 4. Furthermore, transfection with the splicing isoform containing exon 4 suppressed the Q/R editing in primary cultured cerebellar granule neurons. Thus, our study revealed a coupling between an RNA editing and a distant alternative splicing in the Tmem63b pre-mRNA, in which the splicing plays a dominant role. Finally, physiological analysis showed that the splicing and the editing coordinately regulate Ca(2+) permeability and osmosensitivity of channel proteins, which may contribute to their functions in the brain. |
