Processing of Pre-Messenger RNA

描述(由申请人提供)：替代的前信使核糖核酸剪接显著促进了脊椎动物的遗传多样性。这一建议旨在了解替代前mRNA剪接调控的潜在机制。或者，前mRNA的剪接区的特征是存在由剪接因子识别的剪接增强子或沉默序列元件。我们的工作集中在四个前mRNA剪接系统，涉及不同类型的调控元件和剪接因子。要研究的RNA调控序列元件包括：1)刺激外显子包含的富含C/A的外显子增强子，刺激外显子包含和调节5‘剪接位点使用的富含G/A的外显子增强子，调节5’剪接位点使用的富含G的内含子增强子，以及刺激剪接和剪接体组装的富含C的内含子元件。实验被描述为：1)继续表征识别这些RNA元件的因子，2)识别和表征识别元件结合因子来调节剪接的因子，3)确定RNA解旋酶在选择性剪接中的作用，以及4)研究选择性剪接和转录延长相关联的假设。

DESCRIPTION (provided by applicant): Alternative pre-mRNA splicing contributes significantly to genetic diversity in vertebrates. This proposal is aimed at understanding the mechanisms underlying the regulation of alternative pre-mRNA splicing. Alternatively spliced regions of a pre-mRNA are characterized by the presence of splicing enhancer or silencer sequence elements recognized by splicing factors. Our work concentrates on four systems of pre-mRNA splicing that involve different types of regulatory elements and splicing factors. Included in the RNA regulatory sequence elements to be studied are: 1) C/A-rich exon enhancers that stimulate exon inclusion, G/A-rich exon enhancers that stimulate exon inclusion and regulate 5' splice site usage, G-rich intron enhancers that regulate 5' splice site usage, and C-rich intron elements that stimulate splicing and spliceosome assembly. Experiments are described to: 1) continue characterization of the factors that recognize these RNA elements, 2) identify and characterize factors that recognize element-binding factors to regulate splicing, 3) determine the role of RNA helicases in alternative splicing and 4) investigate the hypothesis that alternative splicing and transcriptional elongation are linked.