mRNA degradation in mammalian cells

哺乳动物细胞中 mRNA 降解

• 批准号: 227158-2007
• 负责人: Lee, ChowHwee
• 金额: $ 2.04万
• 依托单位: University of Northern British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=362240
• 关键词: mRNA; degradation; mammalian; cells

Genetic information is stored in the form of DNA found in a cell compartment called the nucleus.  This genetic information has to be transported out of the nucleus into the extra-nuclear cytoplasm where gene products or proteins are made.  Messenger ribonucleic acids or mRNAs are the bio-molecules that carry the genetic information from DNA in the nucleus to the cytoplasm.  mRNAs which carry the genetic code for each gene are then used for the synthesis of proteins.  The proteins then carry out most of the important biochemical functions of the cells.  The amount of proteins is directly dependent on the amount of mRNAs.  Excessive or insufficient amounts of certain proteins due to changes in mRNA levels can lead to diseases.  The amount of mRNA is in large part determined by the rate of its degradation.  An understanding of how mRNA is degraded is therefore important for generating basic knowledge of how mRNA degradation machinery works, as well as for revealing information on the pathogenesis of some diseases.  It is widely believed that mRNAs from eukaryotes, including mammals, are degraded primarily from ends of the molecule.  mRNA is also known to be degraded via cleavage in the middle of the molecule - a process known as endonucleolytic cleavage.  However, little is known about the enzymes (endonucleases) that cleave mammalian mRNAs endonucleolytically and what role they play in controlling mRNA abundance in cells.  Our laboratory has recently purified, characterized, and identified at least two mammalian endonucleases, syntaxin18 and RNase1, that can cleave c-myc mRNA in test tubes.  Syntaxin18 is involved in the mechanism of protein movement in cells but it has not been previously described as an endonuclease.  The major goal of our research is to determine whether syntaxin18 and RNase1 can control mRNA abundance in cells.  This will help us in understanding the significance of endonucleolytic cleavage in controlling mRNA abundance.  In addition, such knowledge has the potential in leading to the use of these enzymes or their properties in applied research.

遗传信息以DNA的形式储存在细胞核中。这些遗传信息必须从细胞核运输到核外细胞质中，在那里基因产物或蛋白质被制造出来。信使核糖核酸或mrna是携带遗传信息从细胞核中的DNA到细胞质的生物分子。携带每个基因遗传密码的信使rna随后被用于蛋白质合成。然后，这些蛋白质执行细胞中大部分重要的生化功能。蛋白质的数量直接取决于mrna的数量。由于mRNA水平的变化，某些蛋白质的过量或不足可导致疾病。mRNA的数量在很大程度上取决于其降解的速度。因此，了解mRNA如何降解对于了解mRNA降解机制如何工作的基本知识以及揭示某些疾病的发病机制非常重要。人们普遍认为，包括哺乳动物在内的真核生物的mrna主要是从分子末端降解的。mRNA也可以通过分子中间的裂解来降解，这一过程被称为核内溶解裂解。然而，对哺乳动物mRNA的内切酶（内切酶）及其在控制细胞mRNA丰度中的作用知之甚少。我们的实验室最近纯化、表征和鉴定了至少两种哺乳动物内切酶，syntaxin18和RNase1，它们可以在试管中切割c-myc mRNA。Syntaxin18参与了细胞中蛋白质运动的机制，但它以前没有被描述为一种核酸内切酶。我们研究的主要目的是确定syntaxin18和RNase1是否可以控制细胞中mRNA的丰度。这将有助于我们理解核内分裂在控制mRNA丰度中的意义。此外，这些知识有可能导致在应用研究中使用这些酶或它们的性质。