Alternative splicing of telomerase catalytic subunit hTERT generated by apoptotic endonuclease EndoG induces human CD4+ T cell death

Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4+ and CD8+ T lymphocytes. Overexpression of EndoG in CD4+ T cells down-regulated the expression of the active full-length hTERT variant and up-regulated expression of the non-active spliced variant. A reduction in full-length hTERT transcripts down-regulated telomerase activity. Long-term in vitro cultivation of EndoG-overexpressing CD4+ T cells led to dramatically shortened telomeres, conversion of cells into a replicative senescence state, and activation of the BCL2/BAX-associated apoptotic pathway finally leading to cell death. These data indicated the participation of EndoG in alternative mRNA splicing of the telomerase catalytic subunit hTERT, regulation of telomerase activity and determination of cell fate. © 2017 Elsevier GmbH

Авторы
Zhdanov D.D. 1, 2 , Vasina D.A. 2 , Grachev V.A. 2 , Orlova E.V.3 , Orlova V.S. 2 , Pokrovskaya M.V.1 , Alexandrova S.S.1 , Sokolov N.N.1
Издательство
Elsevier GmbH
Номер выпуска
7
Язык
Английский
Страницы
653-664
Статус
Опубликовано
Том
96
Год
2017
Организации
  • 1 Laboratory of Medical Biotechnology, Institute of Biomedical Chemistry, Moscow, Russian Federation
  • 2 Peoples Friendship University of Russia, Moscow, Russian Federation
  • 3 Institute of Theoretical and Experimental Biophysics, Puschino, Moscow region, Russian Federation
Ключевые слова
EndoG; hTERT; T cells; Telomerase; Transfection
Дата создания
19.10.2018
Дата изменения
19.10.2018
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/5291/