REGULATION OF ALTERNATIVE PRE-MRNA PROCESSING BY SMALL NUCLEOLAR RNAS

小核仁 RNA 对替代性前 mRNA 加工的调节

• 批准号: 7720904
• 负责人: Stefan Stamm
• 金额: $ 7.37万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720904
• 关键词: Alternative Splicing; Computer Retrieval of Information on Scientific Projects Database; Defect; Drug Delivery Systems; Funding; Gene Targeting; Genes; Genetic; Grant; Heterogeneous Nuclear RNA; Individual; Institution; Knowledge; Life; Masks; Molecular; Obesity; Pattern; Prader-Willi Syndrome; Process; Protein Overexpression; RNA Splicing; Regulation; Regulatory Element; Research; Research Personnel; Resources; Role; Site; Small Nucleolar RNA; Small RNA; Source; Textbooks; United States National Institutes of Health; Work; base; innovation; mRNA Precursor; novel

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. The objective of the project is to determine how the loss of small nucleolar RNA (snoRNA) expression contributes to the Prader-Willi syndrome, the most frequent genetic cause for life-threatening obesity. We will determine which alternative splicing patterns are influenced by the snoRNAs missing in individuals with Prader-Willi syndrome and elucidate the molecular basis by which one of these snoRNAs, HBII-52, influences alternative splicing patterns. The central hypothesis is that snoRNAs missing in individuals with Prader- Willi syndrome regulate alternative splicing by masking splicing regulatory elements on pre-mRNAs. Thus these snoRNAs regulate expression of numerous genes by changing their alternative splicing patterns. The rationale for the proposed research is that the genes regulated by these snoRNAs represent drug targets for treatment of the Prader-Willi syndrome. We use overexpression of snoRNA-expressing constructs to validate bioinformatically predicted target genes. The proposed work is innovative, because it shows a complete new role for snoRNAs in the regulation of alternative pre-mRNA splicing. It may well change the current 'textbook knowledge' that snoRNAs only regulate non-mRNAs. The proposed research is significant because it would show a novel role of snoRNAs, identify the molecular defects in Prader-Willi syndrome and help to predict the influence of small RNAs on splice site selection.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的目的是确定小核仁RNA（SNORNA）表达的丧失如何促进prader-willi综合征，这是威胁生命的肥胖症最常见的遗传原因。我们将确定哪些替代剪接模式受Prader-Willi综合征个体中缺失的ssisnas的影响，并阐明了这些snornas HBII-52中的一种分子基础影响替代剪接模式。中心假设是，在prader-willi综合征中缺少的ssshornas通过掩盖剪接调节元件在MRNA上调节替代剪接。因此，这些snornas通过改变其替代剪接模式来调节众多基因的表达。拟议研究的理由是，这些snoRNA调节的基因代表了治疗prader-willi综合征的药物靶标。我们使用表达SNORNA构建体的过表达来验证生物信息预测的靶基因。拟议的工作是创新的，因为它在调节替代性mRNA剪接的调节中显示出了全新的作用。它很可能会改变当前的“教科书知识”，即snornas只能调节非MRNA。拟议的研究之所以重要，是因为它将显示出snornas的新作用，确定prader-willi综合征中的分子缺陷，并有助于预测小型RNA对剪接位点选择的影响。