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

  • 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
Keywords: caspase-2; alternative splicing; splice switching oligonucleotide; enzymatic activity

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.

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Published
2019-09-30
Section
EXPERIMENTAL RESEARCH