| Autor: |
D. V. Grishin, D. D. Zhdanov, Yulia A. Gladilina, Nikolay N. Sokolov, Vladimir A. Grachev, Vadim S. Pokrovsky, Anna A. Plyasova, M. V. Pokrovskaya, Svetlana S. Alexandrova, V. S. Orlova |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Biochimie. 157:158-176 |
| ISSN: |
0300-9084 |
| DOI: |
10.1016/j.biochi.2018.11.020 |
| Popis: |
Apoptotic endonucleases act cooperatively to fragment DNA and ensure the irreversibility of apoptosis. However, very little is known regarding the potential regulatory links between endonucleases. Deoxyribonuclease 1 (DNase I) inactivation is caused by alternative splicing (AS) of DNase I pre-mRNA skipping exon 4, which occurs in response to EndoG overexpression in cells. The current study aimed to determine the role of EndoG in the regulation of DNase I mRNA AS and the modulation of its enzymatic activity. A strong correlation was identified between the EndoG expression levels and DNase I splice variants in human lymphocytes. EndoG overexpression in CD4+ T cells down-regulated the mRNA levels of the active full-length DNase I variant and up-regulated the levels of the non-active spliced variant, which acts in a dominant-negative fashion. DNase I AS was induced by the translocation of EndoG from mitochondria into nuclei during the development of apoptosis. The DNase I spliced variant was induced by recombinant EndoG or by incubation with EndoG-digested cellular RNA in an in vitro system with isolated cell nuclei. Using antisense DNA oligonucleotides, we identified a 72-base segment that spans the adjacent segments of exon 4 and intron 4 and appears to be responsible for the AS. DNase I-positive CD4+ T cells overexpressing EndoG demonstrated decreased progression towards bleomycin-induced apoptosis. Therefore, EndoG is an endonuclease with the unique ability to inactivate another endonuclease, DNase I, and to modulate the development of apoptosis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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