mRNA degradation in mammalian cells

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中转移到核外的细胞质中，在那里产生基因产物或蛋白质。 信使核糖核酸或mRNA是将遗传信息从细胞核中的DNA携带到细胞质中的生物分子。 携带每个基因遗传密码的mRNA然后用于蛋白质的合成。 然后，蛋白质执行细胞的大多数重要生化功能。 蛋白质的量直接取决于mRNA的量。 由于mRNA水平的变化，某些蛋白质的过量或不足可能导致疾病。 mRNA的量在很大程度上取决于其降解速率。 因此，了解mRNA是如何降解的，对于产生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信息非常重要。 普遍认为，来自真核生物（包括哺乳动物）的mRNA主要从分子的末端降解。 还已知mRNA通过分子中间的切割而降解，这一过程称为内切核酸切割。 然而，很少有人知道的酶（内切核酸酶），切割哺乳动物mRNA的内切核酸，以及它们在控制细胞中的mRNA丰度发挥什么作用。 我们的实验室最近纯化，表征，并确定至少两种哺乳动物核酸内切酶，syntaxin 18和RNase 1，可以在试管中切割c-myc mRNA。 Syntaxin 18参与细胞中蛋白质运动的机制，但它以前没有被描述为核酸内切酶。 我们研究的主要目的是确定syntaxin 18和RNase 1是否可以控制细胞中mRNA的丰度。 这将有助于我们理解核酸内切酶切在控制mRNA丰度中的重要性。 此外，这些知识有可能导致在应用研究中使用这些酶或其特性。

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.