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

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• 作者：D. D. Zhdanov ; D. A. Vasina ; V. S. Orlova…
• 关键词：EndoG ; telomerase ; hTERT ; alternative splicing ; CaCo ; 2
• 刊名：Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：10
• 期：4
• 页码：310-321
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Bioorganic Chemistry; Medicinal Chemistry;
• 出版者：Pleiades Publishing
• ISSN：1990-7516
• 卷排序：10

文摘

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.