PRP8, A CRITICAL PRE-MRNA SPLICING FACTOR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 前体mRNA剪接对于真核基因表达是关键的，并且剪接中的错误导致至少15%的人类遗传病症，例如视网膜色素变性、脊髓性肌萎缩、强直性肌营养不良、弗雷泽综合征、II型家族性孤立性生长激素缺乏症、囊性纤维化、血小板无力症、I型遗传性酪氨酸血症、利氏脑脊髓病、β-地中海贫血、马凡综合征和桑德霍夫病。 我们对前体mRNA剪接的分子机制了解得越透彻，就越有可能在不影响正常剪接的情况下纠正导致遗传疾病的异常剪接。 Prp 8是一种重要的前mRNA剪接因子，人Prp 8的突变会导致严重形式的视网膜色素变性，这是一种常染色体显性遗传疾病，可导致视力逐渐丧失和失明。 我们已经结晶的Prp 8域，并打算确定该域的晶体结构。 了解Prp 8在前mRNA剪接和视网膜色素变性中的结构和功能可能会导致视网膜色素变性和其他遗传疾病的潜在治疗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pre-mRNA splicing is critical for eukaryotic gene expression and errors in splicing contribute to at least 15% of human genetic disorders, such as Retinitis Pigmentosa, Spinal Muscular Atrophy, Myotonic Dystrophy, Frasier Syndrome, Familial Isolated Growth Hormone Deficiency Type II, Cystic Fibrosis, Glanzmann Thrombasthenia, Hereditary Tyrosinemia Type I, Leigh's Encephalomyelopathy, Beta-Thalassemia, Marfan Syndrome, and SandHoff Disease. The more thoroughly we understand the molecular mechanism of pre-mRNA splicing, the more likely we can correct aberrant splicing that cause genetic disorders without affecting normal splicing. Prp8 is a critical pre-mRNA splicing factor and mutations in human Prp8 cause a severe form of Retinitis Pigmentosa, an autosomal dominant genetic disorder that leads to progressive loss of vision and blindness. We have crystallized a domain of Prp8 and intend to determine the crystal structure of this domain. Understanding the structure and function of Prp8 in pre-mRNA splicing and Retinitis Pigmentosa may lead to potential treatment for Retinitis Pigmentosa and other genetic disorders.