title: [Apoptotic endonuclease EndoG induces alternative splicing of telomerase catalytic subunit hTERT and death of tumor cells].
abstract: 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.
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia; Ecological Faculty, Peoples Friendship University of Russia, Moscow, Russia.
authors.forename: D D
authors.initials: DD
authors.lastname: Zhdanov
authors.affiliation: Ecological Faculty, Peoples Friendship University of Russia, Moscow, Russia.
authors.forename: D A
authors.initials: DA
authors.lastname: Vasina
authors.affiliation: Ecological Faculty, Peoples Friendship University of Russia, Moscow, Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Orlova
authors.affiliation: "Viorin" LLC, Moscow, Russia.
authors.forename: V Y
authors.initials: VY
authors.lastname: Gotovtseva
authors.affiliation: "Viorin" LLC, Moscow, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Bibikova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Pokrovsky
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Pokrovskaya
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: S S
authors.initials: SS
authors.lastname: Aleksandrova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: N N
authors.initials: NN
authors.lastname: Sokolov
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis; D018938:Caco-2 Cells; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: C509186:TERT protein, human; D019098:Telomerase; D004706:Endodeoxyribonucleases; C052391:endonuclease G
keywords: EndoG; alternative splicing; hTERT; telomerase