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.

凋亡核酸内切酶协同作用使DNA片段化并确保细胞凋亡的不可逆性。但是，关于核酸内切酶之间潜在的调控联系还知之甚少。脱氧核糖核酸酶1（DNase I）失活是由DNase I pre-mRNA跳过外显子4的选择性剪接（AS）引起的，它是响应EndoG在细胞中的过表达而发生的。当前的研究旨在确定EndoG在DNase I mRNA AS的调节及其酶活性调节中的作用。在人类淋巴细胞中，EndoG表达水平与DNase I剪接变体之间存在很强的相关性。CD4 ^+中的EndoG过表达T细胞下调了活性全长DNase I变体的mRNA水平，并上调了非活性剪接变体的水平，后者以显性负性方式起作用。DNase I AS是由EndoG在细胞凋亡发展过程中从线粒体向细胞核的易位诱导的。通过重组EndoG或与EndoG消化的细胞RNA在具有分离细胞核的体外系统中孵育来诱导DNase I剪接变体。使用反义DNA寡核苷酸，我们确定了一个72个碱基的片段，该片段跨越外显子4和内含子4的相邻片段，并且似乎是AS的原因。DNase I阳性CD4 ⁺过度表达EndoG的T细胞显示出减少的博莱霉素诱导的细胞凋亡进程。因此，EndoG是一种核酸内切酶，具有使另一种核酸内切酶DNase I失活并调节细胞凋亡发展的独特能力。