Center for Food Safety and Applied Nutrition, Division of Biotechnology and GRAS Notice Review, U.S. Food and Drug Administration, College Park, MD 20740, USA.
J Biochem Mol Toxicol. 2010 May-Jun;24(3):195-216. doi: 10.1002/jbt.20325.
In recent years, the discovery of small ncRNAs (noncoding RNAs) has unveiled a slew of powerful riboregulators of gene expression. So far, many different types of small ncRNAs have been described. Of these, miRNAs (microRNAs), siRNAs (small interfering RNAs), and piRNAs (Piwi-interacting RNAs) have been studied in more detail. A significant fraction of genes in most organisms and tissues is targets of these small ncRNAs. Because these tiny RNAs are turning out to be important regulators of gene and genome expression, their aberrant expression profiles are expected to be associated with cellular dysfunction and disease. In fact, an ever-increasing number of studies have implicated miRNAs and siRNAs in human health and disease ranging from metabolic disorders to diseases of various organ systems as well as various forms of cancer. Nevertheless, despite the flurry of research on these small ncRNAs, many aspects of their biology still remain to be understood. The following discussion focuses on some aspects of the biogenesis and function of small ncRNAs with major emphasis on miRNAs since these are the most widespread endogenous small ncRNAs that have been called "micromanagers" of gene expression. Their emerging significance in toxicology is also discussed.
近年来,小分子 ncRNAs(非编码 RNA)的发现揭示了一系列强大的基因表达核糖调控因子。到目前为止,已经描述了许多不同类型的小分子 ncRNAs。其中,miRNAs(microRNAs)、siRNAs(small interfering RNAs)和 piRNAs(Piwi-interacting RNAs)已经得到了更详细的研究。在大多数生物体和组织中,这些小分子 ncRNAs 的靶基因数量相当可观。由于这些微小的 RNA 是基因和基因组表达的重要调控因子,它们的异常表达谱预计与细胞功能障碍和疾病有关。事实上,越来越多的研究表明,miRNAs 和 siRNAs 与人类健康和疾病有关,从代谢紊乱到各种器官系统的疾病以及各种形式的癌症。然而,尽管对这些小分子 ncRNAs 的研究层出不穷,但它们的生物学仍有许多方面尚未得到理解。下面的讨论集中在小分子 ncRNAs 的生物发生和功能的某些方面,主要强调 miRNAs,因为它们是最广泛存在的内源性小分子 ncRNAs,被称为基因表达的“微观管理者”。还讨论了它们在毒理学中的新兴意义。