RNA decay and processing activities of the RNA exosome

摘要 RNA外切体在多种ncRNAs的3‘端加工中起着重要作用 并且还负责mRNAs和nc RNAs的3‘至5’降解。通过 优先降解异常的mRNAs和ncRNAs它还保持了总体 基因表达的保真度。鉴于RNA外切体在多种生物中的中心作用 在RNA加工和降解反应中，它被要求用于 细胞存活率。我们研究的长期目标是更好地理解 RNA外切体如何执行其不同的功能。 RNAexosome是一个由10个亚基组成的复合体，整体呈甜甜圈状 结构。其中9个亚基是催化不活跃的，构成了大多数 甜甜圈。第10个亚基与甜甜圈的一个开口相关联，并赋予两个3‘ RNA外体复合体上的5‘外切核糖核酸酶和内切核酸酶活性。在……里面 在过去的10年里，在理解结构和结构方面取得了很大进展 核糖核酸外切体的生物化学。 虽然分离的Rrp44或RNA外切体在体外具有核酸酶活性，但在 VIVO严格要求有十几种其他蛋白质。尽管很明显这些RNA 外切体辅助因子控制rna外切体的活性和特异性，这些 辅因实现这一点基本上是完全未知的。该计划的总体目标 建议的研究是解决RNA外体辅助因子如何调节其在 活体活动。我们将重点介绍Ski7和RRP6，这是三个RNA外显体中的两个 已知的与RNA外切体直接相互作用的辅因子。无论是遗传还是 生化数据表明，它们之所以重要，部分是因为它们在 与额外的RNA外切体辅助因子的相互作用。

Abstract The RNA exosome plays important roles in 3' end processing of a variety of ncRNAs and is also responsible for 3' to 5' degradation of both mRNAs and nc RNAs. By preferentially degrading aberrant mRNAs and ncRNAs it also maintains the overall fidelity of gene expression. Given the central role of the RNA exosome in a wide variety of RNA processing and degradation reactions, it is not surprising that it is required for cell viability. The long tern goal of our research is to achieve a greater understanding of how the RNA exosome carries out its diverse functions. The RNA exosome is a 10-subunit complex that adopts an overall donut-shaped structure. Nine of the subunits are catalytically inactive, and form the majority of the donut. The 10th subunit is associated with one opening of the donut and confers both 3' to 5' exoribonuclease and endoribonuclease activity on the RNA exosome complex. In the past 10 years much progress has been made in understanding the structure and biochemistry of the RNA exosome. Although isolated Rrp44 or the RNA exosome has nuclease activity in vitro, activity in vivo strictly requires over a dozen other proteins. Although it is clear that these RNA exosome cofactors control the activity and specificity of the RNA exosome, how these cofactors achieve this is essentially completely unknown. The overall goal of the proposed research is to resolve how the RNA exosome cofactors mediate its in vivo activities. We will focus on Ski7 and Rrp6, two of the three RNA exosome cofactors that are known to directly interact with the RNA exosome. Both genetic and biochemical data suggest that they are important in part because they mediate interaction with additional RNA exosome cofactors.