Apoptotic Endonuclease EndoG Induces Alternative Splicing of Telomerase TERT Catalytic Subunit, Caspase-2, DNase I, and BCL-x in Human, Murine, and Rat CD4+ T Lymphocytes
- Authors: Zhdanov D.D.1, Gladilina Y.A.1, Grishin D.V.1, Pokrovsky V.S.1,2, Pokrovskaya M.V.1, Aleksandrova S.S.1, Sokolov N.N.1
-
Affiliations:
- Orekhovich Institute of Biomedical Chemistry
- Blokhin Cancer Research Center
- Issue: Vol 44, No 1 (2018)
- Pages: 90-103
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/228825
- DOI: https://doi.org/10.1134/S1068162018010181
- ID: 228825
Cite item
Abstract
Apoptotic endonuclease EndoG plays a key role in the alternative splicing of mRNA of human TERT telomerase catalytic subunit. The aim of this work was to test the ability of EndoG to induce alternative splicing of mRNA of other genes and in other organisms. To determine new mRNA splice-variants, EndoG overexpression was induced in human, mouse and rat CD4+-T-lymphocytes followed by sequencing of total RNA of these cells. Sequencing results showed that besides TERT, EndoG induced alternative splicing of deoxyribonuclease I (DNase I), caspase-2 (Casp-2) and BCL-x. The expression level of EndoG strongly correlated with mRNA splicing-variants of TERT, DNase I, Casp-2, and BCL-x in intact CD4+-T cells of healthy donors as well as different lines of mice and rats. EndoG overexpression induced down-regulation of fulllength mRNAs of TERT, DNase I, Casp-2, and BCL-x and up-regulation of their short-length mRNAs. Alternative splicing of studied mRNAs resulted in down-regulation of enzymatic activity of proteins in vitro and in vivo. The results of this work confirm the ability of endonuclease EndoG to induce alternative splicing of several mRNAs in human, mice and rats.
About the authors
D. D. Zhdanov
Orekhovich Institute of Biomedical Chemistry
Author for correspondence.
Email: zhdanovdd@mail.ru
Russian Federation, Moscow, 119121
Y. A. Gladilina
Orekhovich Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, Moscow, 119121
D. V. Grishin
Orekhovich Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, Moscow, 119121
V. S. Pokrovsky
Orekhovich Institute of Biomedical Chemistry; Blokhin Cancer Research Center
Email: zhdanovdd@mail.ru
Russian Federation, Moscow, 119121; Moscow, 115478
M. V. Pokrovskaya
Orekhovich Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, Moscow, 119121
S. S. Aleksandrova
Orekhovich Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, Moscow, 119121
N. N. Sokolov
Orekhovich Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
Russian Federation, Moscow, 119121