Mechanisms for quality control of RNA in mammalian cells

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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.