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系统分析转录后基因表达。

Systematic analysis of posttranscriptional gene expression.

机构信息

University Program in Genetics and Genomics, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.

出版信息

Wiley Interdiscip Rev Syst Biol Med. 2010 Mar-Apr;2(2):162-180. doi: 10.1002/wsbm.54.

Abstract

Recent systems studies of gene expression have begun to dissect the layers of regulation that underlie the eukaryotic transcriptome, the combined consequence of transcriptional and posttranscriptional events. Among the regulatory layers of the transcriptome are those of the ribonome, a highly dynamic environment of ribonucleoproteins in which RNA-binding proteins (RBPs), noncoding regulatory RNAs (ncRNAs) and messenger RNAs (mRNAs) interact. While multiple mRNAs are coordinated together in groups within the ribonome of a eukaryotic cell, each individual type of mRNA consists of multiple copies, each of which has an opportunity to be a member of more than one modular group termed a posttranscriptional RNA operon or regulon (PTRO). The mRNAs associated with each PTRO encode functionally related proteins and are coordinated at the levels of RNA stability and translation by the actions of the specific RBPs and noncoding regulatory RNAs. This article examines the methods that led to the elucidation of PTROs and the coordinating mechanisms that appear to regulate the RNA components of PTROs. Moreover, the article considers the characteristics of the dynamic systems that drive PTROs and how mRNA components are bound collectively in physical 'states' to respond to cellular perturbations and diseases. In conclusion, these studies have challenged the extent to which cellular mRNA abundance can inform investigators of the functional status of a biological system. We argue that understanding the ribonome has greater potential for illuminating the underlying coordination principles of growth, differentiation, and disease.

摘要

最近的基因表达系统研究开始剖析真核转录组的调控层,转录和转录后事件的综合结果。转录组的调控层之一是核糖核蛋白体,这是一个核糖核酸结合蛋白 (RBP)、非编码调控 RNA (ncRNA) 和信使 RNA (mRNA) 相互作用的高度动态环境。虽然在真核细胞的核糖核蛋白体中,多个 mRNA 被协调在一起成组,但每个单独类型的 mRNA 由多个副本组成,每个副本都有机会成为多个模块组(称为转录后 RNA 操纵子或调控子 (PTRO))的成员。与每个 PTRO 相关的 mRNA 编码功能相关的蛋白质,并通过特定 RBP 和非编码调节 RNA 的作用在 RNA 稳定性和翻译水平上进行协调。本文探讨了阐明 PTRO 及其协调机制的方法,这些机制似乎调节 PTRO 的 RNA 成分。此外,本文还考虑了驱动 PTRO 的动态系统的特征,以及 mRNA 成分如何以物理“状态”集体结合以响应细胞扰动和疾病。总之,这些研究挑战了细胞 mRNA 丰度在多大程度上能为研究人员提供生物系统功能状态的信息。我们认为,理解核糖核蛋白体更有潜力阐明生长、分化和疾病的潜在协调原则。

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