Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT


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Abstract

Human telomerase catalytic subunit hTERT is subjected to alternative splicing results in loss of its function and leads to decrease of telomerase activity. However, very little is known about the mechanism of hTERT pre-mRNA alternative splicing. Apoptotic endonuclease EndoG is known to participate this process. The aim of this study was to determine the role of EndoG in regulation of hTERT alternative splicing. Increased expression of β-deletion splice variant was determined during EndoG overexpression in CaCo-2 cell line, after EndoG treatment of cell cytoplasm and nuclei as well as after nuclei incubation with EndoG digested cell RNA. hTERT alternative splicing was induced by 47-mer RNA oligonucleotide in naked nuclei and in cells after transfection. Identified long non-coding RNA, that is the precursor of 47-mer RNA oligonucleotide. Its size is 1754 nucleotides. Based on the results the following mechanism was proposed. hTERT pre-mRNA is transcribed from coding DNA strand while long non-coding RNA is transcribed from template strand of hTERT gene. EndoG digests long non-coding RNA and produces 47-mer RNA oligonucleotide complementary to hTERT pre-mRNA exon 8 and intron 8 junction place. Interaction of 47-mer RNA oligonucleotide and hTERT pre-mRNA causes alternative splicing.

About the authors

D. D. Zhdanov

Institute of Biomedical Chemistry; Ecological Faculty

Author for correspondence.
Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121; Moscow

D. A. Vasina

Institute of Biomedical Chemistry

Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121

E. V. Orlova

Institute of Theoretical and Experimental Biophysics

Email: zhdanovdd@mail.ru
Russian Federation, Pushchino

V. S. Orlova

Ecological Faculty

Email: zhdanovdd@mail.ru
Russian Federation, Moscow

M. V. Pokrovskaya

Institute of Biomedical Chemistry

Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121

S. S. Aleksandrova

Institute of Biomedical Chemistry

Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121

N. N. Sokolov

Institute of Biomedical Chemistry

Email: zhdanovdd@mail.ru
Russian Federation, ul. Pogodinskaya 10, Moscow, 119121

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