3' end formation of human type I and II collagen mRNAs

人 I 型和 II 型胶原 mRNA 的 3 末端形成

• 批准号: 7169265
• 负责人: CAROL S LUTZ
• 金额: $ 7.37万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-15 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7169265
• 关键词: end; formation; human; type; II

DESCRIPTION (provided by applicant): We have a long-standing interest in how eukaryotic mRNA 3' ends are formed. Regulation of gene expression can be accomplished by regulating polyadenylation. We have combined this interest in polyadenylation with an interest in human collagen types I and II. Collagen plays a key role in normal cartilage development and skeletal morphogenesis. We have recently discovered and published that human COL1A2 polyadenylation is regulated by cis-acting elements present in the 3' untranslated region (3' UTR) of the COL1A2 mRNA, and that these elements influence the 3' end processing efficiency. Human COL1A1 and COL2A1 we have now discovered also contain these cis-acting elements. Based upon these findings, this project proposes to investigate the mechanism of regulation of polyadenylation of all these type I and II collagen pre-mRNAs. These investigations will expand our goal of better understanding the expression of collagens, and how mutations and abnormal gene expression regulation can initiate a disease state. Our specific aims for this project are: 1) To identify all the cis-acting elements involved in 3' polyadenylation site usage in the human collagen genes COL1A1, COL1A2, and COL2A1 and 2) To determine what trans-acting factor(s) bind to these cis-acting elements. First, we will identify cis-acting elements by deletion and site-directed mutagenesis, and examine their ability to affect polyadenylation efficiency both in vitro and in vivo. Second, protein factors that bind to these cis-acting signals will be explored and characterized. Determination of these protein factors will provide us with clues as to the functional significance of cis-acting auxiliary elements. Gaining an understanding of the RNA signals and protein factors involved in regulation of 3' end formation of these human collagen genes will help us to comprehend collagen gene expression regulation, which will in turn lead to novel insights into skeletal defects and other collagen-based diseases.

描述（由申请人提供）：我们对如何形成真核mRNA 3'末端感兴趣。基因表达的调节可以通过调节聚腺苷酸化来实现。我们将对聚腺苷酸化的兴趣与对人类胶原蛋白I和II的兴趣相结合。胶原蛋白在正常软骨发育和骨骼形态发生中起关键作用。我们最近发现并发表了人类COL1A2聚腺苷酸化受到COL1A2 mRNA的3'未翻译区域（3'utr）中的顺式作用元件的调节，并且这些元素会影响3'最终处理效率。人类COL1A1和COL2A1我们现在发现还包含这些顺式作用元素。基于这些发现，该项目提出了研究所有这些I型和II型胶原蛋白PREMRNA的多腺苷酸化调节机制。这些研究将扩大我们更好地理解胶原蛋白表达的目标，以及突变和基因表达异常的调节如何启动疾病状态。我们对该项目的具体目的是：1）确定人类胶原基因COL1A1，COL1A2和COL2A1和2中3'聚烯基化位点使用中涉及的所有顺式作用元件，以确定哪种跨作用因子与这些顺式作用元素结合。首先，我们将通过缺失和定位的诱变来识别顺式作用元件，并检查其在体外和体内影响聚腺苷酸化效率的能力。其次，将探索并表征与这些顺式作用信号结合的蛋白质因子。这些蛋白质因子的确定将为我们提供有关顺式作用辅助元件功能意义的线索。了解这些人类胶原蛋白基因的3'末端形成涉及的RNA信号和蛋白质因子将有助于我们理解胶原蛋白基因表达调节，这反过来又导致对骨骼缺陷和其他基于胶原蛋白的疾病的新见解。