Intracellular localization of apoptotic endonuclease EndoG and splice-variants of telomerase catalytic subunit hTERT

The activity of telomerase catalytic subunit hTERT (human telomerase reverse transcriptase) can be regulated by alternative splicing of its mRNA. The mechanism of hTERT splicing is not understood in detail. Apoptotic endonuclease EndoG is known to participate in this process. In the present work, the intracellular colocalization and mRNA levels of EndoG and hTERT splice-variants in normal and apoptotic cancer cells were studied. We found that the development of apoptosis increased the expression of EndoG and changed the ratio of hTERT splice-variants, which decreased the telomerase activity in the cells. The development of apoptosis was accompanied by changes in the amount of mRNA and in the localization of EndoG and hTERT splice-variants in the cytoplasm, nuclei, and mitochondria of the cells. The suppression of EndoG expression using RNA interference prevented induction of the α+β–splice-variant of hTERT and inhibition of the telomerase activity. A high degree of the intracellular colocalization of EndoG and hTERT was shown. The changes in the expression and localization of EndoG corresponded with changes in the amount and localization of hTERT splice-variants. These data confirm the participation of EndoG in the alternative splicing of mRNA of the telomerase catalytic subunit and in regulation of the telomerase activity. © 2017, Pleiades Publishing, Ltd.

Авторы
Zhdanov D.D. 1, 2 , Pokrovsky V.S. 1, 3 , Orlova E.V.4 , Orlova V.S. 2 , Pokrovskaya M.V.1 , Aleksandrova S.S.1 , Sokolov N.N.1
Журнал
Номер выпуска
8
Язык
Английский
Страницы
894-905
Статус
Опубликовано
Том
82
Год
2017
Организации
  • 1 Orekhovich Institute of Biomedical Chemistry, Moscow, 119121, Russian Federation
  • 2 Ecological Faculty, Russian University of People’s Friendship, Moscow, 117198, Russian Federation
  • 3 Blokhin Russian Cancer Research Center, Moscow, 115478, Russian Federation
  • 4 Institute of Theoretical and Experimental Biophysics, Pushchino, Moscow Region, 142290, Russian Federation
Ключевые слова
alternative splicing; apoptosis; EndoG; hTERT; telomerase
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