Ribonucleic acid turnover in man: RNA catabolites in urine as measure for the metabolism of each of the three major species of RNA

Abstract

1. Urinary excretion of the non-reusable modified RNA catabolites pseudouridine (ψ), 7-methylguanine (m7Gua) and N2,N2-dimethylguanosine (m22Guo) was measured in preterm infants and in adults. The values (in μmol/mmol of creatinine) were: for preterm and ‘small for gestational age’ infants (n = 26; number of samples = 38) ψ = 164 (sd 32), m7Gua = 39.1 (sd 9.0), m22Guo = 10.6 (sd 2.1); for adults (n = 32) ψ = 25.3 (sd 3.1), m7Gua = 4.8 (sd 0.89), m22Guo = 1.53 (sd 0.42). 2. Our measurements were compared with an expectation derived from the average cellular distribution of ψ, m7Gua and m22Guo between rRNA, tRNA and mRNA. m22Guo occurs exclusively in iRNA, ψ in both rRNA and tRNA, and m7Gua in all three RNA classes, in proportions which can be estimated for the steady state. Urinary excretion of ψ and m22Guo should reflect their steady-state distribution, since rRNA and tRNA have been shown to have similar turnover rates in mammalian tissues. 3. We conclude that we can use the excretion of m22Guo to assess whole-body tRNA turnover. Since tRNA contains ψ constant proportion to m22Guo, the proportion of urinary ψ stemming from tRNA can be estimated, and the remainder (~ 60–65%) is an indicator of rRNA turnover. Finally, the excretion of m7Gua far exceeds the proportion predicted to come from rRNA and tRNA. We ascribe this excess (~ 60–70% of the total) to the turnover of the mRNA ‘cap’-structure, which is typical for all higher organisms. mRNA turnover is known to be much higher than that of rRNA or tRNA. 4. Calculated average RNA turnover rates (in μmol day−1 kg−1 body weight) were: for preterm infants 0.1 rRNA, 1.93 tRNA, 2.44 mRNA-‘cap’; for adults 0.037 rRNA, 0.63 tRNA, 0.62 mRNA-‘cap’. 5. Estimation of RNA turnover rates may supplement the hitherto more widely used 15N tracer studies in assessing whole-body metabolic state. Results obtained up to now closely agree with the findings from 15N tracer studies (approximately threefold higher turnover rates in preterm infants than in adults). This is probably correlated with the fact that RNA is intimately involved in all steps of protein synthesis.