Coburn G A, Mackie G A
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
Prog Nucleic Acid Res Mol Biol. 1999;62:55-108. doi: 10.1016/s0079-6603(08)60505-x.
Metabolic instability is a hallmark property of mRNAs in most if not all organisms and plays an essential role in facilitating rapid responses to regulatory cues. This article provides a critical examination of recent progress in the enzymology of mRNA decay in Escherichia coli, focusing on six major enzymes: RNase III, RNase E, polynucleotide phosphorylase, RNase II, poly(A) polymerase(s), and RNA helicase(s). The first major advance in our thinking about mechanisms of RNA decay has been catalyzed by the possibility that mRNA decay is orchestrated by a multicomponent mRNA-protein complex (the "degradosome"). The ramifications of this discovery are discussed and developed into mRNA decay models that integrate the properties of the ribonucleases and their associated proteins, the role of RNA structure in determining the susceptibility of an RNA to decay, and some of the known kinetic features of mRNA decay. These models propose that mRNA decay is a vectorial process initiated primarily at or near the 5' terminus of susceptible mRNAs and propagated by successive endonucleolytic cleavages catalyzed by RNase E in the degradosome. It seems likely that the degradosome can be tethered to its substrate, either physically or kinetically through a preference for monphosphorylated RNAs, accounting for the usual "all or none" nature of mRNA decay. A second recent advance in our thinking about mRNA decay is the rediscovery of polyadenylated mRNA in bacteria. Models are provided to account for the role of polyadenylation in facilitating the 3' exonucleolytic degradation of structured RNAs. Finally, we have reviewed the documented properties of several well-studied paradigms for mRNA decay in E. coli. We interpret the published data in light of our models and the properties of the degradosome. It seems likely that the study of mRNA decay is about to enter a phase in which research will focus on the structural basis for recognition of cleavage sites, on catalytic mechanisms, and on regulation of mRNA decay.
代谢不稳定性是大多数（如果不是所有）生物体中mRNA的一个标志性特性，在促进对调控信号的快速反应中起着至关重要的作用。本文对大肠杆菌中mRNA衰变酶学的最新进展进行了批判性审视，重点关注六种主要酶：核糖核酸酶III、核糖核酸酶E、多核苷酸磷酸化酶、核糖核酸酶II、聚腺苷酸聚合酶和RNA解旋酶。我们对RNA衰变机制的思考取得的第一个重大进展，是由mRNA衰变由多组分mRNA-蛋白质复合物（“降解体”）精心编排这一可能性所推动的。本文讨论了这一发现的影响，并将其发展为mRNA衰变模型，该模型整合了核糖核酸酶及其相关蛋白质的特性、RNA结构在决定RNA对衰变敏感性方面的作用，以及mRNA衰变的一些已知动力学特征。这些模型提出，mRNA衰变是一个矢量过程，主要在易感mRNA的5'末端或其附近启动，并由降解体中核糖核酸酶E催化的连续内切核酸酶切割传播。降解体似乎可以通过对单磷酸化RNA的偏好，在物理上或动力学上与底物相连，这解释了mRNA衰变通常的“全或无”性质。我们对mRNA衰变思考的第二个近期进展是在细菌中重新发现了多聚腺苷酸化的mRNA。本文提供了模型来解释多聚腺苷酸化在促进结构化RNA的3'外切核酸酶降解中的作用。最后，我们回顾了大肠杆菌中几个经过充分研究的mRNA衰变范例的记录特性。我们根据我们的模型和降解体的特性来解释已发表的数据。mRNA衰变的研究似乎即将进入一个阶段，在此阶段，研究将集中在切割位点识别的结构基础、催化机制以及mRNA衰变的调控上。
