FUNCTIONAL ANALYSIS OF CFIM PROTEINS IN GERM CELL ALTERNATIVE POLYADENYLATION

生殖细胞替代聚腺苷酸化中 CFIM 蛋白的功能分析

• 批准号: 7960149
• 负责人: Becky Lynn Sartini
• 金额: $ 2.22万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960149
• 关键词: 3' Untranslated Regions; Accounting; Behavioral Research; Biological Assay; Cells; Computer Retrieval of Information on Scientific Projects Database; Couples; Development; Fibrinogen; Funding; Gene Expression; Gene Expression Regulation; Generations; Germ Cells; Grant; Institution; Male Infertility; Messenger RNA; Molecular; Poly(A) Tail; Polyadenylation; Production; Protein Isoforms; Proteins; RNA Interference; RNA-Binding Proteins; Research; Research Personnel; Resources; Role; Site; Somatic Cell; Source; Spermatogenesis; Study models; Testis; Transcript; Translations; Treatment Failure; United States National Institutes of Health; cell growth regulation; male; sperm cell; sperm function

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. Male infertility accounts for one third of the couples who seek treatment for failure to conceive. Recent research has shown that aberrant regulation of gene expression during spermatogenesis causes decreased sperm function. Alternative polyadenylation, the generation of cell-specific messenger RNA (mRNA) isoforms by poly (A) tail addition, is a hallmark of gene regulation during spermatogenesis. Cleavage factor I (CFIm), comprised of the NUDT21/CPSF5 and CPSF6 subunits, are polyadenylation RNA binding proteins that are highly enriched in male germ cells and contain a shorter 3'untranslated region (UTR) generated by alternative polyadenylation. While the CFIm proteins can direct differential polyadenylation site selection of somatic cell mRNAs, the role of CFIm in producing testis-specific transcripts is unknown. Using RNA interference, we will develop functional studies in a male germ cell line to investigate the hypothesis that CFIm subunits are necessary for male germ cell-specific alternative polyadenylation and subsequent protein translation. Development of a functional assay in this male germ cell line will also establish a model for studying gene expression during spermatogenesis. A greater understanding the molecular and cellular regulation of sperm production holds promise in developing new treatments for male infertility.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 因无法怀孕而寻求治疗的夫妇中，有三分之一患有男性不育症。最近的研究表明，精子发生过程中基因表达的异常调节会导致精子功能下降。选择性聚腺苷酸化，即通过添加聚 (A) 尾部产生细胞特异性信使 RNA (mRNA) 亚型，是精子发生过程中基因调控的标志。切割因子 I (CFIm) 由 NUDT21/CPSF5 和 CPSF6 亚基组成，是多腺苷酸化 RNA 结合蛋白，在雄性生殖细胞中高度富集，并包含由选择性多腺苷酸化产生的较短的 3' 非翻译区 (UTR)。虽然 CFIm 蛋白可以指导体细胞 mRNA 的差异多腺苷酸化位点选择，但 CFIm 在产生睾丸特异性转录物中的作用尚不清楚。利用 RNA 干扰，我们将在雄性生殖细胞系中开展功能研究，以调查 CFIm 亚基对于雄性生殖细胞特异性选择性多聚腺苷酸化和随后的蛋白质翻译所必需的假设。在该雄性生殖细胞系中开发功能测定也将为研究精子发生过程中的基因表达建立模型。更好地了解精子产生的分子和细胞调节有望开发男性不育症的新疗法。