Kurzynska-Kokorniak Anna, Koralewska Natalia, Pokornowska Maria, Urbanowicz Anna, Tworak Aleksander, Mickiewicz Agnieszka, Figlerowicz Marek
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan 61-704, Poland.
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan 61-704, Poland Institute of Computing Science, Poznan University of Technology, Poznan 60-965, Poland
Nucleic Acids Res. 2015 May 19;43(9):4365-80. doi: 10.1093/nar/gkv328. Epub 2015 Apr 16.
There is increasing evidence indicating that the production of small regulatory RNAs is not the only process in which ribonuclease Dicer can participate. For example, it has been demonstrated that this enzyme is also involved in chromatin structure remodelling, inflammation and apoptotic DNA degradation. Moreover, it has become increasingly clear that cellular transcript and protein levels of Dicer must be strictly controlled because even small changes in their accumulation can initiate various pathological processes, including carcinogenesis. Accordingly, in recent years, a number of studies have been performed to identify the factors regulating Dicer gene expression and protein activity. As a result, a large amount of complex and often contradictory data has been generated. None of these data have been subjected to an exhaustive review or critical discussion. This review attempts to fill this gap by summarizing the current knowledge of factors that regulate Dicer gene transcription, primary transcript processing, mRNA translation and enzyme activity. Because of the high complexity of this topic, this review mainly concentrates on human Dicer. This review also focuses on an additional regulatory layer of Dicer activity involving the interactions of protein and RNA factors with Dicer substrates.
越来越多的证据表明，小调节RNA的产生并非核糖核酸酶Dicer能够参与的唯一过程。例如，已经证明这种酶还参与染色质结构重塑、炎症和凋亡性DNA降解。此外，越来越清楚的是，必须严格控制Dicer的细胞转录本和蛋白质水平，因为它们积累的微小变化都可能引发各种病理过程，包括致癌作用。因此，近年来，已经进行了多项研究来确定调节Dicer基因表达和蛋白质活性的因素。结果，产生了大量复杂且常常相互矛盾的数据。这些数据均未经过详尽的综述或批判性讨论。本综述试图通过总结目前关于调节Dicer基因转录、初级转录本加工、mRNA翻译和酶活性的因素的知识来填补这一空白。由于该主题的高度复杂性，本综述主要集中于人类Dicer。本综述还聚焦于Dicer活性的另一个调节层面，即蛋白质和RNA因子与Dicer底物的相互作用。
