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Biochemistry of Small Nucleolar RNAs in Yeast

酵母中小核仁 RNA 的生物化学

基本信息

批准号：
7490522
负责人：
MAURILLE J FOURNIER
金额：
$ 36.41万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-06-01 至 2011-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant) The nucleolus contains scores of small nucleolar RNA-protein complexes (snoRNPs), which modify nucleotides in rRNA (most snoRNPs do this) or participate in processing (cleavage) of prerRNA. The modifying snoRNPs form 2'-O-methylated nucleotides and pseudouridine, mostly in functionally important regions of the ribosome. The effects of these alterations are virtually unknown. The main unanswered question with the processing snoRNPs is their actual role. The proposal has two main aims -designed to answer these important questions. Both build on results from the previous grant. First, we showed that systematic depletion of nucleotide modifications from the reaction center region of the ribosome causes defects in translation. Second, we have affinity-isolated a conserved snoRNP (U14) required for processing and methylation of 18S rRNA, and identified several novel proteins, including factors already tied to ribosome synthesis. The major aims of our application are: 1) To determine the influence of nucleotide modifications in the mRNA decoding center and two other domains that interact dynamically with tRNA in the decoding region, and; 2) To determine the roles of the U14 snoRNP proteins in rRNA processing and modification. Effects of nucleotide modification will be investigated by depleting selected modifications from the target regions and examining ribosome synthesis and function. Studies of the U14 snoRNP will focus initially on defining the roles of the new snoRNP components in ribosome synthesis, by genetic depletion, mutation and affinity isolation strategies. Other goals include describing the assembly, structure and activity of the snoRNP complex. Results from the studies will yield valuable new insights into ribosome synthesis and function, and could shed light on the basis of established links between snoRNPs, aging and cancer.

描述（由申请人提供）核仁含有大量小核仁 RNA-蛋白质复合物 (snoRNP)，它们修饰 rRNA 中的核苷酸（大多数 snoRNP 会这样做）或参与 prerRNA 的加工（切割）。修饰的 snoRNP 形成 2'-O-甲基化核苷酸和假尿苷，主要位于核糖体的功能重要区域。这些改变的影响实际上是未知的。处理 snoRNP 的主要未解决问题是它们的实际作用。该提案有两个主要目标——旨在回答这些重要问题。两者都建立在先前拨款的结果之上。首先，我们发现核糖体反应中心区域的核苷酸修饰的系统性缺失会导致翻译缺陷。其次，我们亲和分离了 18S rRNA 加工和甲基化所需的保守 snoRNP (U14)，并鉴定了几种新的蛋白质，包括已经与核糖体合成相关的因子。我们应用的主要目的是：1）确定核苷酸修饰的影响 mRNA 解码中心和另外两个与 tRNA 动态相互作用的域解码区域，以及； 2) 确定U14 snoRNP蛋白在rRNA加工中的作用和修改。将通过耗尽选定的核苷酸修饰的效果来研究从目标区域进行修饰并检查核糖体合成和功能。研究 U14 snoRNP 最初将重点关注定义新 snoRNP 组件的作用通过遗传耗竭、突变和亲和力分离策略进行核糖体合成。其他目标包括描述 snoRNP 复合物的组装、结构和活性。研究结果将为核糖体合成和功能带来有价值的新见解，并可以阐明 snoRNP、衰老和癌症之间已建立的联系。