mRNA Processing in Reproduction and Fertilization

生殖和受精中的 mRNA 加工

• 批准号: 6926169
• 负责人: Clinton C MacDonald
• 金额: $ 9.37万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6926169
• 关键词: RNA binding protein; animal genetic material tag; binding sites; cell differentiation; cell growth regulation; cell line; gene expression; genetic polymorphism; genetic regulation; genetically modified animals; human genetic material tag; human tissue; in situ hybridization; intermolecular interaction; laboratory mouse; male; meiosis; messenger RNA; polyadenylate; posttranscriptional RNA processing; protein isoforms; protein structure function; sperm; spermatogenesis; western blottings

DESCRIPTION (provided by applicant): We are trying to understand how mRNA polyadenylation occurs in male germ cells in the absence of the canonical AAUAAA polyadenylation signal. We discovered and characterized a variant form of the CstF-64 polyadenylation protein that is expressed at high levels in meiotic and postmeiotic germ cells, and in no other tissue except the brain. This new protein, called "(CstF-64," is the leading candidate to account for AAUAAA-independent polyadenylation in germ cells. Our overall laboratory hypothesis is that (1) the somatic CstF-64 gene (Cstf2) is on the X chromosome in mice and humans, (2) the X-chromosomal CstF-64 is inactivated during male meiosis, (3) since CstF-64 function is essential, an auxiliary CstF-64 gene must be expressed from an autosome, and (4) the auxiliary CstF-64 protein is responsible for AAUAAA-independent polyadenylation of mRNAs in male germ cells and is essential for spermatogenesis. In the previous grant period, we addressed items 1-3 of our hypothesis. The goals of this grant proposal are to address item 4. This Independent Scientist Award (K02) will assist me in accomplishing those goals. Specifically, I am seeking to receive salary support to release me from some or all of my teaching and administrative duties so that I can devote a greater portion of my time to research and career development. For the research portion, I will be able to spend more time in the laboratory myself, and to direct the research of my workers more effectively. For the career development portion, I will be able to attend national and international meetings, and spend short periods visiting laboratories of collaborators to learn new techniques relevant to our work. These activities will be especially helpful, because my background is in biochemistry and not in reproductive biology. The Department of Cell Biology & Biochemistry is an excellent place from which to achieve these goals: the major strength of the Department is in many aspects of reproductive biology, and my colleagues have been exceedingly generous in sharing their ideas and expertise. This environment, supplemented with trips to meetings and visits to collaborators, will provide excellent support for my endeavors.

描述（由申请人提供）：我们试图了解在缺乏典型的AAUAAA多腺苷化信号的情况下，mRNA多腺苷化是如何在男性生殖细胞中发生的。我们发现并表征了CstF-64多腺苷化蛋白的一种变体形式，该蛋白在减数分裂和减数分裂后生殖细胞中高水平表达，除了大脑外，在其他组织中都没有表达。这种名为“（CstF-64）”的新蛋白是解释生殖细胞中不依赖于aauaaa的聚腺苷酸化的主要候选蛋白。我们的总体实验室假设是：(1)体细胞CstF-64基因（Cstf2）在小鼠和人类的X染色体上，(2)X染色体CstF-64在雄性减数分裂期间失活，(3)由于CstF-64的功能是必不可少的，因此辅助的CstF-64基因必须从常染色体中表达，(4)辅助的CstF-64蛋白负责雄性生殖细胞中mrna的aauaaa非依赖性多腺苷化，对精子发生至关重要。在之前的资助期间，我们解决了假设的第1-3项。本奖助金提案的目标是解决第4项。这个独立科学家奖（K02）将帮助我实现这些目标。具体地说，我希望得到工资支持，以免除我部分或全部的教学和行政职责，以便我能把更多的时间用于研究和职业发展。在研究部分，我可以花更多的时间在实验室里，更有效地指导我的工人的研究。在职业发展方面，我将能够参加国内和国际会议，并短期访问合作者的实验室，学习与我们工作相关的新技术。这些活动将会特别有帮助，因为我的背景是生物化学而不是生殖生物学。细胞生物与生物化学系是实现这些目标的绝佳场所：该系的主要优势在于生殖生物学的许多方面，我的同事们非常慷慨地分享了他们的想法和专业知识。这种环境，加上出差开会和拜访合作者，将为我的努力提供极好的支持。