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Article

Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma

  • Authors:
    • Zhaohui Li
    • Yu Tian
    • Nan Tian
    • Xingli Zhao
    • Chao Du
    • Liang Han
    • Haishan Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Cell Biology, College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Surgery Institute, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
  • Pages: 2845-2852
    |
    Published online on: April 8, 2015
       https://doi.org/10.3892/or.2015.3907
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Abstract

Adenosine-to-inosine (A-to-I) RNA editing is the most common type of RNA editing in mammals, and is catalyzed by adenosine deaminases acting on RNA (ADARs). ADAR2 is the main enzyme responsible for A-to-I editing in humans, and A-to-I underediting at the glutamine (Q)/arginine (R) site of the glutamate receptor subunit B (GluR-B) is associated with the pathogenesis and invasiveness of glioma. The level of ADAR2 mRNA expression and the alternative splicing of the ADAR2 pre-mRNA both affect the catalytic activity of ADAR2. However, reports of ADAR2 mRNA expression in glioma are inconsistent. The mechanism regulating ADAR2 pre-mRNA splicing is also unknown. In this study, we explored the deregulation of A-to-I RNA editing in glioma. We confirmed the underediting at the Q/R site of GluR-B mRNA in the glioma cell lines U87, U251 and A172 compared with that in normal human astrocytes (NHAs) HA1800. However, we demonstrated with reverse transcription (RT-PCR) and quantitative PCR (qPCR) that the expression of ADAR2 mRNA was not significantly altered in the glioma cell lines. Three alternative splicing sites are utilized in the glioma cell lines and NHAs: the first, located between exons -1 and 1, causes the inclusion of exon 1a; the second causes the removal of exon 2, which encodes two double-stranded RNA-binding domains; and the third, located between exons 4 and 6, causes the inclusion of alternative exon 5a, introducing a 120-nucleotide coding Alu-repeat sequence in frame. However, the expression ratio of two types of transcripts (with and without exon 5a) was altered in the glioma cells. Transcripts with exon 5a, which generate an ADAR2 isoform with ~50% reduced activity, were predominantly expressed in the glioma cell lines, whereas transcripts without exon 5a were predominantly expressed in the NHAs. From these results, we conclude that this aberrant alternative splicing pattern of ADAR2 downregulates A-to-I editing in glioma.
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Copy and paste a formatted citation
Spandidos Publications style
Li Z, Tian Y, Tian N, Zhao X, Du C, Han L and Zhang H: Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma. Oncol Rep 33: 2845-2852, 2015.
APA
Li, Z., Tian, Y., Tian, N., Zhao, X., Du, C., Han, L., & Zhang, H. (2015). Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma. Oncology Reports, 33, 2845-2852. https://doi.org/10.3892/or.2015.3907
MLA
Li, Z., Tian, Y., Tian, N., Zhao, X., Du, C., Han, L., Zhang, H."Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma". Oncology Reports 33.6 (2015): 2845-2852.
Chicago
Li, Z., Tian, Y., Tian, N., Zhao, X., Du, C., Han, L., Zhang, H."Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma". Oncology Reports 33, no. 6 (2015): 2845-2852. https://doi.org/10.3892/or.2015.3907
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Tian Y, Tian N, Zhao X, Du C, Han L and Zhang H: Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma. Oncol Rep 33: 2845-2852, 2015.
APA
Li, Z., Tian, Y., Tian, N., Zhao, X., Du, C., Han, L., & Zhang, H. (2015). Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma. Oncology Reports, 33, 2845-2852. https://doi.org/10.3892/or.2015.3907
MLA
Li, Z., Tian, Y., Tian, N., Zhao, X., Du, C., Han, L., Zhang, H."Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma". Oncology Reports 33.6 (2015): 2845-2852.
Chicago
Li, Z., Tian, Y., Tian, N., Zhao, X., Du, C., Han, L., Zhang, H."Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma". Oncology Reports 33, no. 6 (2015): 2845-2852. https://doi.org/10.3892/or.2015.3907
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