Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
Cell Cycle. 2010 Feb 15;9(4):840-9. doi: 10.4161/cc.9.4.10829. Epub 2010 Mar 2.
26S proteasome is a large multi-subunit protein complex involved in proteolytic degradation of proteins. In addition to its canonical proteolytic activity, the proteasome is also associated with recently characterized endoribonuclease (endo- RNAse) activity. However, neither functional significance, nor the mechanisms of its regulation are currently known. In this report, we show that 26S proteasome is able to hydrolyze various cellular RNAs, including AU-rich mRNA of c-myc and c-fos. The endonucleolytic degradation of these mRNAs is exerted by one of the 26S proteasome subunits, PSMA5 (alpha5). The RNAse activity of 26S proteasome is differentially affected by various extra-cellular signals. Moreover, this activity contributes to the process of degradation of c-myc mRNA during induced differentiation of K562 cells, and may be controlled by phosphorylation of the adjacent subunits, PSMA1 (alpha6) and PSMA3 (alpha7). Collectively, the data presented in this report suggest a causal link between cell signalling pathways, endo-RNAse activity of the 26S proteasome complex and metabolism of cellular RNAs.
26S 蛋白酶体是一种参与蛋白质降解的大型多亚基蛋白复合物。除了其典型的蛋白水解活性外，蛋白酶体还与最近表征的内切核糖核酸酶（endo-RNAse）活性相关。然而，其功能意义及其调控机制目前尚不清楚。在本报告中，我们表明 26S 蛋白酶体能够水解各种细胞 RNA，包括 c-myc 和 c-fos 的富含 AU 的 mRNA。这些 mRNA 的内切核酸酶降解是由 26S 蛋白酶体的一个亚基 PSMA5（α5）施加的。细胞外信号对 26S 蛋白酶体的 RNA 酶活性有不同的影响。此外，这种活性有助于 K562 细胞诱导分化过程中 c-myc mRNA 的降解过程，并且可能受相邻亚基 PSMA1（α6）和 PSMA3（α7）的磷酸化控制。总的来说，本报告中的数据表明细胞信号通路、26S 蛋白酶体复合物的内切 RNA 酶活性与细胞 RNA 代谢之间存在因果关系。
