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.

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