MRNA SPLICING FACTOR BRR2

前mRNA剪接。去除非编码序列（内含子）的过程 从基因的转录，是必不可少的生存能力，在较高的 真核生物剪接过程涉及数百种蛋白质， 多个RNA种类必须以精确的顺序聚集在一起， 正确的时间，为了删除内含子，没有别的。的 发生的多重重排和构象变化， 剪接被假设是由RNA等介导的 解旋酶，一类解开RNA特定区域的蛋白质。的 本提案的目的是研究特定剪接的作用， 因子Brr2在剪接过程和重排中， 发生在拼接过程中。Brr2中的一个突变阻断了前 mRNA剪接，序列相似性表明它是一种RNA 解旋酶此外，有证据表明，它直接与 U2 snRNP暗示后者可能是它的底物。的 这里提出的实验将鉴定Brr 2的底物。寻找 它的调节剂，并定义了一个假定的dsRNA结合的功能， Brr2中的结构域。这项工作将扩展我们对生物化学的理解， 这类关键的蛋白质，并为未来的研究提供了基础。 解旋酶的结构研究

Pre-mRNA splicing. The process of removing non-coding sequences (introns) from the transcripts of genes, is essential for viability in higher Eukaryotes. The splicing process involves hundreds of proteins and multiple RNA species which must come together in a precise sequence at the correct times, in order to remove the introns and nothing else. The multiple rearrangements and conformational changes that occur during splicing are hypothesized to be mediated by, among other things, RNA helicases, a class of proteins that unwind specific regions of RNA. The goal of this proposal is to investigate the role of a specific splicing factor, Brr2, in the splicing process and in the rearrangements that occur during splicing. One mutation in Brr2 blocks the first step in pre- mRNA splicing, and sequence similarity suggests that it is an RNA helicase. Furthermore, there is evidence that it interacts directly with the U2 snRNP. Implying that the latter may be its substrate. The experiments proposed here will identify the substrate of Brr2. look for its regulators, and define the function of a putative dsRNA-binding domain in Brr2. This work will extend our biochemical understanding of this crucial class of proteins and provide a foundation for future structural studies of helicases.