RNA decay and processing activities of the RNA exosome

摘要 RNA外泌体在多种ncRNA的3'末端加工中起重要作用 并且也负责mRNA和nc RNA的3 ′至5 ′降解。通过 它优先降解异常mRNA和ncRNA，也维持了整体的 基因表达的保真度。鉴于RNA外泌体在多种细胞中的核心作用， RNA加工和降解反应，这并不奇怪，它是必需的， 细胞活力我们研究的长期目标是更好地理解 RNA外泌体如何发挥其多种功能。 RNA外泌体是一个由10个亚基组成的复合体， 结构其中九个亚基是无催化活性的，并形成了大部分的亚基。 甜甜圈第10个亚基与甜甜圈的一个开口相关，并赋予两个3' 至5'核糖核酸外切酶和核糖核酸内切酶对RNA外泌体复合物的活性。在 在过去的10年里，在理解结构方面取得了很大进展， RNA外泌体的生物化学。 尽管分离的Rrp44或RNA外泌体在体外具有核酸酶活性，但在体外的活性与RNA外泌体的活性不同。 体内严格需要十几种其他蛋白质。虽然很明显这些RNA 外泌体辅因子控制RNA外泌体的活性和特异性，这些辅因子是如何控制RNA外泌体的活性和特异性的？ 辅因子实现这一点基本上是完全未知的。的总体目标 拟议的研究是解决RNA外泌体辅因子如何介导其在细胞中的表达。 活体活性我们将重点关注三种RNA外泌体中的两种Ski7和Rrp6， 已知与RNA外泌体直接相互作用的辅因子。遗传和 生化数据表明，它们之所以重要，部分原因是它们介导了 与其他RNA外泌体辅因子的相互作用。

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.