Inhibition of Caspase-2 Activity in Human Jurkat T-cell Lymphoma Cells by Splice Switching Oligonucleotide to its pre-mRNA

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Published: Sep 30, 2019
DOI: https://doi.org/10.18097/BMCRM00108
Keywords:
caspase-2; alternative splicing; splice switching oligonucleotide; enzymatic activity

Main Article Content

D.D. Zhdanov
Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia; Peoples Friendship University of Russia, 6 Miklukho-Maklaya str., Moscow, 117198 Russia
A.A. Plyasova
Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
Yu.A. Gladilina
Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
M.V. Pokrovskaya
Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
S.S. Alexandrova
Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
N.N. Sokolov
Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia

Abstract

Caspase-2 is a key enzyme thinvolved in induction of apoptosis. The caspase-2 level is regulated by alternative splicing (AS) of its mRNA. The aim of this work was to determine the ability of an oligonucleotide complementary to Casp-2 pre-mRNA to induce AS. This oligonucleotide blocked the binding of splicing-regulating proteins to their sites at the end of exon 9 of Casp-2 pre-mRNA, leading to induction of AS of Casp-2 mRNA. The decrease in expression of full-size active splice-variant (Casp-2L) and the increase the expression of a shortened variant (Casp-2S) was demonstrated in human T-cell lymphoma Jurkat cell line. The expression level of total Casp-2 remained unchanged. Disproportion of splice variants of Casp-2 led to inhibition of enzymatic activity of caspase-2.

Article Details

How to Cite
Zhdanov, D., Plyasova, A., Gladilina, Y., Pokrovskaya, M., Alexandrova, S., & Sokolov, N. (2019). Inhibition of Caspase-2 Activity in Human Jurkat T-cell Lymphoma Cells by Splice Switching Oligonucleotide to its pre-mRNA. Biomedical Chemistry: Research and Methods, 2(3), e00108. https://doi.org/10.18097/BMCRM00108
Issue
Vol. 2 No. 3 (2019)
Section
EXPERIMENTAL RESEARCH

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