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. 2016 Mar;62(3):239-50.
doi: 10.18097/PBMC20166203239.

[Apoptotic endonuclease EndoG induces alternative splicing of telomerase catalytic subunit hTERT and death of tumor cells]

[Article in Russian]
D D Zhdanov  1 , D A Vasina  2 , V S Orlova  2 , V Y Gotovtseva  3 , M V Bibikova  3 , V S Pokrovsky  4 , M V Pokrovskaya  4 , S S Aleksandrova  4 , N N Sokolov  4
Affiliations

[Apoptotic endonuclease EndoG induces alternative splicing of telomerase catalytic subunit hTERT and death of tumor cells]

[Article in Russian]
D D Zhdanov et al. Biomed Khim. 2016 Mar.

Abstract
in English, Russian

Telomerase activity is known to be regulated by alternative splicing of its catalytic subunit hTERT (human Telomerase Reverse Transcriptase) mRNA. Induction of 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 apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. Strong correlation was found between expression of EndoG and hTERT splice-variants in 12 colon cancer cell lines. Overexpression of EndoG in СаСо-2 cells downregulated the expression of active full-length hTERT variant and upregulated non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, dramatically shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. These data indicated the participation of EndoG in alternative splicing of mRNA of telomerase catalytic subunit, regulation of telomerase activity and cell fate.

Aktivnost' telomerazy reguliruetsia al'ternativnym splaĭsingom mRNK ee kataliticheskoĭ sub"edinitsy hTERT (human Telomerase Reverse Transcriptase). Uvelichenie kolichestva neaktivnoĭ splaĭs-formy hTERT ingibiruet telomeraznuiu aktivnost'. V nastoiashchee vremia mekhanizm splaĭsinga hTERT izuchen nedostatochno polno. Tsel'iu raboty bylo izuchenie vliianiia apoptoticheskoĭ éndonukleazy EndoG na al'ternativnyĭ splaĭsing hTERT i aktivnost' telomerazy. V kletkakh 12 liniĭ raka kishechnika cheloveka vyiavlena vzaimosviaz' mezhdu urovniami ékspressii EndoG i splaĭs-variantov hTERT. Sverkhékspressiia EndoG v kletkakh SaSo-2 vyzyvala snizhenie ékspressii polnorazmernogo aktivnogo varianta hTERT i uvelichenie ékspressii splaĭs-varianta. Umen'shenie kolichestva polnorazmernogo varianta hTERT privodilo k snizheniiu telomeraznoĭ aktivnosti, ukorocheniiu dliny telomer do kriticheskikh znacheniĭ, perekhodu kletok v sostoianie replikativnogo stareniia, aktivatsii apoptoticheskikh protsessov i gibeli kletok. Éti dannye ukazyvaiut na uchastie EndoG v protsesse al'ternativnogo splaĭsinga mRNK kataliticheskoĭ sub"edinitsy telomerazy i reguliatsii telomeraznoĭ aktivnosti.

Keywords: EndoG; alternative splicing; hTERT; telomerase.

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