Biogenesis of Small RNAs

描述(申请人提供)：真核生物中的大量小RNA 细胞包括剪接体U SnRNAs，信号的RNA成分 识别颗粒、端粒酶RNA、转移RNA和5S核糖体RNA。 虽然人们对其中许多RNA的功能了解很多，但对这些RNA的功能知之甚少 已知这些RNA是如何从更大的前体、折叠和 组装成具有功能的RNA-蛋白质复合体。建议的工作重点 以下是在Small的生物发生中发挥关键作用的几种蛋白质 RNA。一种正在研究的蛋白质，La自身抗原，是第一个 在合成后立即与许多小RNA结合。实验 在酵母中，酿酒酵母提出了酵母La蛋白Lhplp 起到分子伴侣的作用，帮助新生的 体内转录的小RNA。其他正在研究的蛋白质是 Sm和Sm-like蛋白家族，这是稳定所需的 剪接体U小核RNA积聚。我们的研究解决了 三个广泛的问题。首先，Lhplp的绑定机制是什么 新生的RNA促进了小RNA的加工、折叠和RNP组装？ 第二，类Sm蛋白如何在生物发生和功能中发挥作用 它们的相关RNA呢？第三，Sm蛋白如何结合它们的底物RNA，以及 还有哪些蛋白质在SnRNP组装过程中发挥作用？建议数 研究应该通过提供急需的信息来扩展我们对RNA生物发生的知识 对RNA折叠和RNP组装过程的洞察。此外，由于 La和Sm蛋白都是慢性粒细胞白血病患者的主要自身抗原 系统性红斑狼疮，我们的工作可能提供为什么蛋白质 在小RNA生物发生的最早步骤中的功能是 自身免疫反应。

DESCRIPTION (provided by applicant): The numerous small RNAs in eukaryotic cells include the spliceosomal U snRNAs, the RNA component of the signal recognition particle, the telomerase RNA, transfer RNAs and 5S ribosomal RNA. Although much is known about the functions of many of these RNAs, far less is known about how these RNAs are processed from larger precursors, folded arid assembled into functional RNA-protein complexes. The focus of the work proposed here are several proteins that play critical roles in the biogenesis of small RNAs. One protein under study, the La autoantigen, is the first protein that associates with many small RNAs immediately after their synthesis. Experiments in the yeast Saccharomyces cerevisiae have suggested the yeast La protein Lhplp functions as a molecular chaperone to facilitate the correct fate of newly transcribed small RNAs in vivo. Other proteins under study are members of the Sm and Sm-like families of proteins, which are required for the stable accumulation of the spliceosomal U small nuclear RNAs. Our research addresses three broad questions. First, what are the mechanisms by which binding by Lhplp to nascent RNAs facilitates small RNA processing, folding and RNP assembly? Second, how do Sm-like proteins contribute to the biogenesis and function of their associated RNAs? Third, how do Sm proteins bind their substrate RNAs, and what other proteins function in the snRNP assembly process? The proposed studies should expand our knowledge of RNA biogenesis by providing much needed insights into the processes of RNA folding and RNP assembly. Furthermore, since both the La and the Sm proteins are major autoantigens in patients with systemic lupus erythematosus, our work may provide clues as to why proteins that function in the earliest steps of small RNA biogenesis are targets of the autoimmune response.