Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Endocrinology. 2010 Apr;151(4):1391-7. doi: 10.1210/en.2009-1250.
Gene expression starts with transcription and is followed by multiple posttranscriptional processes that carry out the splicing, capping, polyadenylation, and export of each mRNA. Interest in posttranscriptional regulation has increased recently with explosive discoveries of large numbers of noncoding RNAs such as microRNAs, yet posttranscriptional processes depend largely on the functions of RNA-binding proteins as well. Glucocorticoid nuclear receptors are classical examples of environmentally reactive activators and repressors of transcription, but there has also been a significant increase in studies of the role of posttranscriptional regulation in endocrine responses, including insulin and insulin receptors, and parathyroid hormone as well as other hormonal responses, at the levels of RNA stability and translation. On the global level, the transcriptome is defined as the total RNA complement of the genome, and thereby, represents the accumulated levels of all expressed RNAs, because they are each being produced and eventually degraded in either the nucleus or the cytoplasm. In addition to RNA turnover, the many underlying posttranscriptional layers noted above that follow from the transcriptome function within a dynamic ribonucleoprotein (RNP) environment of global RNA-protein and RNA-RNA interactions. With the exception of the spliceosome and the ribosome, thousands of heterodispersed RNP complexes wherein RNAs are dynamically processed, trafficked, and exchanged are heterogeneous in size and composition, thus providing significant challenges to their investigation. Among the diverse RNPs that show dynamic features in the cytoplasm are processing bodies and stress granules as well as a large number of smaller heterogeneous RNPs distributed throughout the cell. Although the localization of functionally related RNAs within these RNPs are responsive to developmental and environmental signals, recent studies have begun to elucidate the global RNA components of RNPs that are dynamically coordinated in response to these signals. Among the factors that have been found to affect coordinated RNA regulation are developmental signals and treatments with small molecule drugs, hormones, and toxins, but this field is just beginning to understand the role of RNA dynamics in these responses.
基因表达始于转录,随后是多个转录后过程,这些过程执行每个 mRNA 的剪接、加帽、多聚腺苷酸化和输出。最近,随着大量非编码 RNA(如 microRNA)的发现,人们对转录后调控的兴趣大增,但转录后过程在很大程度上依赖于 RNA 结合蛋白的功能。糖皮质激素核受体是环境反应性转录激活剂和抑制剂的经典范例,但在激素反应中,包括胰岛素和胰岛素受体、甲状旁腺激素以及其他激素反应,研究翻译后调控在 RNA 稳定性和翻译水平上的作用也显著增加。在全局水平上,转录组被定义为基因组的总 RNA 补充,因此代表了所有表达 RNA 的累积水平,因为它们都在细胞核或细胞质中产生并最终降解。除了 RNA 周转外,上述许多潜在的转录后层是从转录组在动态核糖核蛋白 (RNP) 环境中的功能中产生的,该环境包含全局 RNA-蛋白和 RNA-RNA 相互作用。除了剪接体和核糖体外,数以千计的异质 RNP 复合物中,RNA 动态加工、运输和交换,大小和组成不同,因此对它们的研究提出了重大挑战。在细胞质中显示动态特征的多种 RNP 中,有处理体和应激颗粒以及大量分布在整个细胞中的较小异质 RNP。虽然这些 RNP 内功能相关 RNA 的定位对发育和环境信号有反应,但最近的研究已经开始阐明对这些信号动态协调的 RNP 的全局 RNA 成分。已发现影响协调 RNA 调节的因素包括发育信号和小分子药物、激素和毒素的处理,但该领域才刚刚开始理解 RNA 动力学在这些反应中的作用。