Mechanisms for quality control of RNA in mammalian cells

RNA合成中自发错误的基础水平估计为每个残基10^<-5>，这大大高于DNA复制的基础水平，并且在有氧状态下转录的保真度会更差。这意味着即使在正常细胞中也会合成许多错误的蛋白质。此外，当RNA碱基被内部或外部试剂修饰时，转录保真度会降低。在这些修饰中，8-氧鸟嘌呤（8-oxoG）尤其重要，因为这种修饰的碱基会导致碱基错配。研究表明，RNA聚合酶在DNA的腺嘌呤残基对面掺入8-oxoG可引起部分表型抑制。在这种情况下，虽然大多数蛋白质是正常的，但一些产物是不正常的。大多数产生的错误蛋白质可能是无活性的，但有些可能表现出可能导致某些细胞功能紊乱的显性特征，从而可能导致灾难性的后果。8-oxoG可以通过将氧化的鸟嘌呤核苷酸结合到RNA中，也可以通过直接氧化RNA中的鸟嘌呤碱基在RNA中形成。在大肠杆菌中，MutT蛋白的作用是阻止前一过程，而PNP蛋白似乎参与后一过程。类似的机制似乎在哺乳动物细胞中起作用，但与细菌细胞相比，情况要复杂得多。至少有两种具有不同底物偏好的蛋白MTH1和NUDT5参与前一个过程，还有两种不同类型的蛋白PNP和YB-1参与后一个过程。

The basal level of spontaneous errors in RNA synthesis is estimated to be 10^<-5> per residue, which is considerably higher than that for DNA replication, and the fidelity of transcription would be worse in an aerobic state. This means that numerous erroneous proteins are synthesized even in normal cells. Furthermore, the transcriptional fidelity would become lower when the RNA bases are modified by internal or external agents. Among such modifications, 8-oxoguanine (8-oxoG) is particularly important since this modified base causes base mispairing. It has been shown that the incorporation of 8-oxoG opposite the adenine residues of DNA by RNA polymerase causes a partial phenotypic suppression. In this case, although the majority of the proteins made are normal, some of the products are abnormal. Most of the erroneous proteins produced may be inactive, but some may exhibit dominant characteristics that can cause disorders of some cellular functions, which could thus lead to catastrophic consequences.8-oxoG can be formed in RNA by the incorporation of oxidized guanine nucleotide into RNA and also by the direct oxidation of the constituent guanine base in the RNA. In E coli, the MutT protein functions to prevent the former process while the PNP protein appears to be involved in the latter. Similar mechanisms seem to function in mammalian cells, but the situations are much more complex in comparison to the bacterial ones. At least two proteins with different substrate preferences, MTH1 and NUDT5, are involved in the former process, and also two different types of proteins, PNP and YB-1, are implicated with the latter process.