Mechanisms for quality control of RNA in mammalian cells

RNA合成中自发错误的基本水平估计为每个残基10^-5；-5；这比DNA复制的水平高得多，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大量错误的蛋白质。此外，当RNA碱基被内部或外部因素修饰时，转录保真度会变得更低。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。结果表明，RNA聚合酶掺入与DNA腺嘌呤残基相反的8-oxoG会导致部分表型抑制。在这种情况下，尽管制造的大部分蛋白质是正常的，但也有一些产品是异常的。产生的大多数错误蛋白质可能是不活跃的，但一些可能表现出显性特征，导致某些细胞功能紊乱，从而导致灾难性的后果。8-oxoG可以通过将氧化的鸟嘌呤核苷酸掺入RNA中以及通过RNA中的鸟嘌呤碱基的直接氧化在RNA中形成。在大肠杆菌中，MUT蛋白起到阻止前一种过程的作用，而PNP蛋白似乎参与了后一种过程。类似的机制似乎在哺乳动物细胞中起作用，但与细菌相比，情况要复杂得多。至少有两种具有不同底物偏好的蛋白质MTH1和NUDT5参与了前一过程，另外两种不同类型的蛋白质PNP和YB-1也参与了后一过程。

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.