Possible use of urinary modified RNA metabolites in the measurement of RNA turnover in the human body.

Abstract

Modified building blocks are found in rRNA, tRNA and mRNA. Apart from pseudouridine these are mostly base- or ribose-methylated nucleosides. If these compounds are neither recycled nor degraded, they should be quantitatively excreted. For pseudouridine (Weissman et al., 1962; Dugaiczyk & Eiler, 1966) and 7-methylguanine (Craddock, Mattocks & Magee, 1968), urinary excretion has been shown to be quantitative. Since the turnover rates of rRNA and tRNA, which contain most of the modified nucleosides, are similar within a given tissue, compounds found only in these two classes of RNA should appear in urine in approximately the proportions in which they are present in the body. Using pseudouridine as internal standard, we show this indeed to be likely for one of the major RNA catabolites in human urine, N2,N2-dimethylguanosine, a compound present only in tRNA. By contrast, 7-methylguanine is excreted in threefold larger amounts than can be explained by joint provenance from tRNA and rRNA only; the remainder we assume to come from the 'cap' structure of mRNA, known for its high turnover. We suggest that one can use the urinary excretion of pseudouridine, N2,N2-dimethylguan(os)ine and 7-methylguanine to assess the whole-body turnover rates in man of rRNA, tRNA and mRNA, respectively. Such data may be useful to define whole-body metabolic activity.