REGULATED POLYADENYLATION OF MESSENGER RNA

描述：(改编自申请者的摘要)这位调查员 此前的研究表明，从非洲爪哇白蛋白中分离出的 细胞质或核组分具有异常短且离散的17个残基 Poly(A)尾巴。随后发现了一个类似的短Poly(A)尾巴 转录后调控的其他mRNAs的数量 与白蛋白mRNA相似，证明了短的聚(A)尾巴是 未加工核白蛋白Pre-RNA的特征。短Poly(A)尾部结果 从多聚(A)限制元件(PLE)的存在中获得的 白蛋白基因。一项基于数据的搜索已经确定了数百个患有PLE的基因 相似的元素，这位调查者演示了PLE的功能 在编码HIV-EP2/SchNurri 2的基因中，锌指转录因子 这激活了整合的HIV-1前病毒的转录。整体而言 结果表明，至少存在两类多聚腺苷酸化的mRNAs； 那些带着200+多聚(A)尾巴离开原子核的，以及那些离开原子核的 核具离散的，&lt；20个核苷酸的聚(A)尾巴。这项提案的总体目标是 是为了确定负责调节PolyA尾巴的分子机制 长度，并定义此过程对 带有短Poly(A)尾巴的mRNAs的代谢和翻译。具体目标 因此，该项目的目的是1)确定和描述核PLE 结合蛋白(PLE-BP)；2)确定细胞的功能相互作用 为了阐明PLE和PLE-BP的调控机制 Poly(A)尾部长度；以及3)确定 将Poly(A)限制在20个核苷酸以下 核，对稳定和不稳定的mRNAs的周转以及对 翻译。

DESCRIPTION: (Adapted from the applicant's abstract) This investigator previously showed that Xenopus albumin mRNA isolated from either the cytoplasmic or nuclear fractions has an unusually short and discrete 17 residue poly(A) tail. A similarly short poly(A) tail was subsequently identified on a number of other mRNAs that were post-transcriptionally regulated in a manner similar to the albumin mRNA and demonstrated that the short poly(A) tail was feature of unprocessed nuclear albumin pre-RNA. The short poly(A) tail results from the presence of a poly(A)-limiting element (PLE) in the terminal exon of the albumin gene. A data based search has identified hundreds of genes with PLE like elements and this investigator demonstrated the functionality of the PLE in the gene encoding the HIV-EP2/Schnurri 2, a zinc finger transcription factor that activates transcription of the integrated HIV-1 provirus. The overall results suggest that there are at least two categories of polyadenylated mRNAs; those that exit the nucleus with a 200+ poly(A) tail, and those that exit the nucleus with a discrete, <20 nt poly(A) tail. The overall goal of this proposal is to define the molecular mechanism responsible for regulating poly(A) tail length, and to define the functional consequences of this process on the metabolism and translation of mRNAs with short poly(A) tails. The specific aims of this project therefore seek to 1) identify and characterize the nuclear PLE binding protein (PLE-BP); 2) to determine the functional interactions of the PLE-BP in order to elucidate the mechanisms by which PLE and PLE-BP regulate poly(A) tail length; and 3) to determine the functional consequences of limiting poly(A) to less than 20 nucleotides on export of mRNA from the nucleus, on the turnover of both stable and unstable mRNAs, as well as on translation.