Mechanisms of deadenylation-dependent decay.
Mechanisms of deadenylation-dependent decay.
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DOI：
10.1002/wrna.40
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发表时间：
2011-03
影响因子：
7.3
通讯作者：
Shyu, Ann-Bin
中科院分区：
文献类型：
--
作者：
Chen, Chyi-Ying A.;Shyu, Ann-Bin
mRNA的降解在基因表达的调节和mRNA生物合成的质量控制中起着重要作用。到目前为止，真核生物中几乎所有主要的mRNA降解途径都是由去腺苷化启动的，即，mRNA 3′ poly（A）尾缩短。脱腺苷酸化通常是mRNA降解和翻译沉默的限速步骤，使其成为这两个过程的重要控制点。在这篇综述中，我们讨论了真核生物中mRNA去腺苷化的基本原理。我们使用哺乳动物细胞中几种主要的mRNA衰变途径来说明去腺苷依赖性mRNA衰变的机制和调控，包括3′非翻译区（UTR）中富含AU的元件（战神）指导的衰变，蛋白质编码区中不稳定元件介导的快速衰变，检测和降解无义mRNA（即，NMD）、由miRNAs指导的衰变以及稳定信息的默认衰变途径。哺乳动物mRNA去腺苷化涉及两个连续的阶段，分别由PAN 2-PAN 3和CCR 4-CAF 1复合物介导。脱帽发生在去腺苷化之后，并且如果初始去腺苷化受损，则可以作为触发mRNA衰变的备用机制。此外，我们还讨论了去腺苷化如何影响RNA加工体（P体）的动力学，在那里不可翻译的mRNA可以被降解或储存。各种deadenylation依赖的mRNA衰变途径的机制的可能模型也进行了讨论。
Degradation of mRNAs plays an essential role in modulation of gene expression and in quality control of mRNA biogenesis. Nearly all major mRNA decay pathways characterized thus far in eukaryotes are initiated by deadenylation, i.e., shortening of the mRNA 3′ poly(A) tail. Deadenylation is often a rate-limiting step for mRNA degradation and translational silencing, making it an important control point for both processes. In this review, we discuss the fundamental principles that govern mRNA deadenylation in eukaryotes. We use several major mRNA decay pathways in mammalian cells to illustrate mechanisms and regulation of deadenylation-dependent mRNA decay, including decay directed by AU-rich elements (AREs) in the 3′ untranslated region (UTR), the rapid decay mediated by destabilizing elements in protein-coding regions, the surveillance mechanism that detects and degrades nonsense-containing mRNA (i.e., NMD), the decay directed by miRNAs, and the default decay pathway for stable messages. Mammalian mRNA deadenylation involves two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes, respectively. Decapping takes place after deadenylation and may serve as a backup mechanism to trigger mRNA decay if initial deadenylation is compromised. In addition, we discuss how deadenylation impacts the dynamics of RNA processing bodies (P-bodies), where non-translatable mRNAs can be degraded or stored. Possible models for mechanisms of various deadenylation-dependent mRNA decay pathways are also discussed.
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