Open AccessInhibition of Caspase-2 Activity in Human Jurkat T-cell Lymphoma Cells by Splice Switching Oligonucleotide to its pre-mRNA
Author(s) -
Dmitry Zhdanov,
Anna A. Plyasova,
Yulia A. Gladilina,
M. V. Pokrovskaya,
S. Alexandrova,
Н. Н. Соколов
Publication year - 2019
Publication title -
biomedical chemistry: research and methods
Language(s) - English
Resource type - Journals
ISSN - 2618-7531
DOI - 10.18097/bmcrm00108
Subject(s) - jurkat cells , casp , rna splicing , microbiology and biotechnology , oligonucleotide , messenger rna , splice , caspase 2 , exon , alternative splicing , biology , chemistry , apoptosis , caspase , rna , gene , programmed cell death , genetics , biochemistry , t cell , protein structure , immune system , protein structure prediction
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.