Biogenesis of Small RNAs

描述（由申请人提供）：真核生物中的许多小RNA 细胞包括剪接体U snRNA，信号的RNA成分 识别颗粒、端粒酶RNA、转移RNA和5S核糖体RNA。 尽管对这些RNA的功能了解很多， 我们知道这些RNA是如何从更大的前体，折叠和 组装成功能性RNA-蛋白质复合物。提出的工作重点 这里有几种蛋白质在小的生物发生中起着关键作用， RNA。正在研究的一种蛋白质，La自身抗原，是第一种 在合成后立即与许多小RNA结合。实验 在酿酒酵母中，已经提出了酵母La蛋白Lhplp 作为一种分子伴侣的功能，以促进正确的命运， 在体内转录小RNA。正在研究的其他蛋白质是 Sm和Sm样蛋白质家族，这是稳定 剪接体U小核RNA的积累。我们的研究解决 三大问题。首先，Lhplp的结合机制是什么？ 促进小RNA加工、折叠和RNP组装？ 第二，Sm样蛋白是如何促进细胞的生物发生和功能的？ 相关的RNA？第三，Sm蛋白如何结合其底物RNA， 在snRNP组装过程中还有哪些蛋白质起作用？拟议 研究应该通过提供急需的信息来扩展我们对RNA生物发生的认识。 深入了解RNA折叠和RNP组装的过程。此外，由于 La和Sm蛋白都是原发性肝癌患者的主要自身抗原， 系统性红斑狼疮，我们的工作可能会提供线索，为什么蛋白质 在小RNA生物合成的最早阶段起作用的蛋白质， 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.