Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT
- Authors: Zhdanov D.D.1,2, Vasina D.A.1, Orlova E.V.3, Orlova V.S.2, Pokrovskaya M.V.1, Aleksandrova S.S.1, Sokolov N.N.1
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Affiliations:
- Institute of Biomedical Chemistry
- Ecological Faculty
- Institute of Theoretical and Experimental Biophysics
- Issue: Vol 11, No 2 (2017)
- Pages: 154-165
- Section: Article
- URL: https://journals.rcsi.science/1990-7508/article/view/197767
- DOI: https://doi.org/10.1134/S1990750817020135
- ID: 197767
Cite item
Abstract
Human telomerase catalytic subunit hTERT is subjected to alternative splicing results in loss of its function and leads to decrease of telomerase activity. However, very little is known about the mechanism of hTERT pre-mRNA alternative splicing. Apoptotic endonuclease EndoG is known to participate this process. The aim of this study was to determine the role of EndoG in regulation of hTERT alternative splicing. Increased expression of β-deletion splice variant was determined during EndoG overexpression in CaCo-2 cell line, after EndoG treatment of cell cytoplasm and nuclei as well as after nuclei incubation with EndoG digested cell RNA. hTERT alternative splicing was induced by 47-mer RNA oligonucleotide in naked nuclei and in cells after transfection. Identified long non-coding RNA, that is the precursor of 47-mer RNA oligonucleotide. Its size is 1754 nucleotides. Based on the results the following mechanism was proposed. hTERT pre-mRNA is transcribed from coding DNA strand while long non-coding RNA is transcribed from template strand of hTERT gene. EndoG digests long non-coding RNA and produces 47-mer RNA oligonucleotide complementary to hTERT pre-mRNA exon 8 and intron 8 junction place. Interaction of 47-mer RNA oligonucleotide and hTERT pre-mRNA causes alternative splicing.
Keywords
About the authors
D. D. Zhdanov
Institute of Biomedical Chemistry; Ecological Faculty
Author for correspondence.
Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121; Moscow
D. A. Vasina
Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121
E. V. Orlova
Institute of Theoretical and Experimental Biophysics
Email: zhdanovdd@mail.ru
Russian Federation, Pushchino
V. S. Orlova
Ecological Faculty
Email: zhdanovdd@mail.ru
Russian Federation, Moscow
M. V. Pokrovskaya
Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121
S. S. Aleksandrova
Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121
N. N. Sokolov
Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121
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