mRNA degradation in mammalian cells

遗传信息以DNA的形式存储在一个被称为细胞核的细胞室中。这种遗传信息必须从细胞核传输到核外细胞质，在那里制造基因产物或蛋白质。信使核糖核酸或mRNAs是将遗传信息从细胞核中的DNA携带到细胞质的生物分子。携带每个基因遗传密码的mRNAs随后被用于蛋白质的合成。然后，这些蛋白质执行细胞的大部分重要生化功能。蛋白质的数量直接取决于mRNAs的数量。由于信使核糖核酸水平的变化，某些蛋白质的含量过多或不足都可能导致疾病。信使核糖核酸的数量在很大程度上取决于它的降解速度。因此，了解信使核糖核酸是如何降解的，对于产生信使核糖核酸降解机制的基本知识以及揭示某些疾病的发病机制是很重要的。人们普遍认为，包括哺乳动物在内的真核生物的mRNAs主要是从分子的末端降解的。人们还知道，通过分子中间的裂解--这一过程被称为内切核裂解--信使核糖核酸被降解。然而，对于以内切方式裂解哺乳动物mRNAs的酶(内切酶)以及它们在控制细胞内mRNA量方面所起的作用，人们知之甚少。我们实验室最近已经提纯、鉴定和鉴定了至少两种哺乳动物内切酶，Synaxin18和RNase1，它们可以在试管中裂解c-myc mRNA。Synaxin18参与了细胞内蛋白质运动的机制，但以前并未被描述为核酸内切酶。我们研究的主要目的是确定Synaxin18和RNase1是否可以控制细胞中的mRNA丰度。这将有助于我们理解核酸内切在控制mRNA丰度方面的意义。此外，这种知识有可能导致在应用研究中使用这些酶或它们的性质。

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.