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Distant coupling between RNA editing and alternative splicing of the osmosensitive cation channel Tmem63b.
Wu, Dan; Zang, Yan-Yu; Shi, Yong-Yun; Ye, Chang; Cai, Wen-Min; Tang, Xiao-Hui; Zhao, Liyun; Liu, Yong; Gan, Zhenji; Chen, Gui-Quan; Xu, Yun; Yang, Jian-Jun; Shi, Yun Stone.
Afiliación
  • Wu D; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School
  • Zang YY; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School
  • Shi YY; Department of Orthopaedics, Luhe People's Hospital Affiliated to Yangzhou University, Nanjing, China.
  • Ye C; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School
  • Cai WM; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School
  • Tang XH; Department of Anesthesiology and Perioperative Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; School of Medicine, Southeast University, Nanjing, China.
  • Zhao L; Translational Science and Clinical Biomarker, BeiGene (Shanghai) Co., Ltd., Shanghai, China.
  • Liu Y; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan, China.
  • Gan Z; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School
  • Chen GQ; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School
  • Xu Y; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing, China; Institute for Brain Sciences, Nanjing University, Nanjing, China.
  • Yang JJ; Department of Anesthesiology and Perioperative Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: yjyangjj@126.com.
  • Shi YS; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School
J Biol Chem ; 295(52): 18199-18212, 2020 12 25.
Article en En | MEDLINE | ID: mdl-33100268
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 ∼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 Ca2+ permeability and osmosensitivity of channel proteins, which may contribute to their functions in the brain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Precursores del ARN / Canales de Calcio / Adenosina Desaminasa / Exones / Proteínas de Unión al ARN / Edición de ARN / Empalme Alternativo Límite: Animals / Female / Humans / Male Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Precursores del ARN / Canales de Calcio / Adenosina Desaminasa / Exones / Proteínas de Unión al ARN / Edición de ARN / Empalme Alternativo Límite: Animals / Female / Humans / Male Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos