Rutjes S A, van der Heijden A, Utz P J, van Venrooij W J, Pruijn G J
Department of Biochemistry, University of Nijmegen, P. O. Box 9101, NL-6500 HB Nijmegen, The Netherlands.
J Biol Chem. 1999 Aug 27;274(35):24799-807. doi: 10.1074/jbc.274.35.24799.
We have investigated the fate of the RNA components of small ribonucleoprotein particles in apoptotic cells. We show that the cytoplasmic Ro ribonucleoprotein-associated Y RNAs are specifically and rapidly degraded during apoptosis via a caspase-dependent mechanism. This is the first study describing the selective degradation of a specific class of small structural RNA molecules in apoptotic cells. Cleavage and subsequent truncation of Y RNAs was observed upon exposure of cells to a variety of apoptotic stimuli and were found to be inhibited by Bcl-2, zinc, and several caspase inhibitors. These results indicate that apoptotic degradation of Y RNAs is dependent on caspase activation, which suggests that the nucleolytic activity responsible for hY RNA degradation is activated downstream of the caspase cascade. The Y RNA degradation products remain bound by the Ro60 protein and in part also by the La protein, the only two proteins known to be stably associated with intact Ro ribonucleoprotein particles. The size of the Y RNA degradation products is consistent with the protection from degradation of the most highly conserved region of the Y RNAs by the bound Ro60 and La proteins. Our results indicate that the rapid abrogation of the yet unknown function of Y RNAs might be an early step in the systemic deactivation of the dying cell.
我们研究了凋亡细胞中小核糖核蛋白颗粒的RNA成分的命运。我们发现，细胞质中与Ro核糖核蛋白相关的Y RNA在凋亡过程中通过一种半胱天冬酶依赖性机制被特异性且快速地降解。这是第一项描述凋亡细胞中一类特定的小结构RNA分子选择性降解的研究。在细胞暴露于多种凋亡刺激后，观察到Y RNA的切割及随后的截短，并且发现其受到Bcl-2、锌和几种半胱天冬酶抑制剂的抑制。这些结果表明Y RNA的凋亡降解依赖于半胱天冬酶的激活，这表明负责hY RNA降解的核酸水解活性在半胱天冬酶级联反应的下游被激活。Y RNA降解产物仍与Ro60蛋白结合，部分还与La蛋白结合，这是已知仅有的两种与完整Ro核糖核蛋白颗粒稳定相关的蛋白。Y RNA降解产物的大小与结合的Ro60和La蛋白对Y RNA最保守区域的降解保护作用一致。我们的结果表明，Y RNA未知功能的快速丧失可能是垂死细胞系统性失活的早期步骤。
