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

Abstract

Urinary excretion of the non-reusable modified RNA catabolites pseudouridine (psi), 7-methylguanine (m7Gua) and N2,N2-dimethylguanosine (m2(2)Guo) was measured in preterm infants and in adults. The values (in mumol/mmol of creatinine) were: for preterm and 'small for gestational age' infants (n = 26; number of samples = 38) psi = 164 (SD 32), m7Gua = 39.1 (SD 9.0), m2(2)Guo = 10.6 (SD 2.1); for adults (n = 32) psi = 25.3 (SD 3.1), m7Gua = 4.8 (SD 0.89), m2(2)Guo = 1.53 (SD 0.42). Our measurements were compared with an expectation derived from the average cellular distribution of psi, m7Gua and m2(2)Guo between rRNA, tRNA and mRNA. m2(2)Guo occurs exclusively in tRNA, psi 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 psi and m2(2)Guo should reflect their steady-state distribution, since rRNA and tRNA have been shown to have similar turnover rates in mammalian tissues. We conclude that we can use the excretion of m2(2)Guo to assess whole-body tRNA turnover. Since tRNA contains psi in a constant proportion to m2(2)Guo, the proportion of urinary psi stemming from tRNA can be estimated, and the remainder (approximately 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 (approximately 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 or rRNA or tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of urinary nucleosides by direct injection and coupled-column high-performance liquid chromatography

“…The mean levels of 14 nucleosides in normal urines have been established (Table 5). The results were well correlated with those obtained by other authors [14,18,19,23]. Fig.…”

“…Therefore, any disorder of RNA turnover alters the levels of modified nucleosides. A number of studies have examined their biomedical significance as possible biomarkers for cancer [3][4][5][6][7][8][9], AIDS [10][11][12] and for the whole-body turnover of RNAs [13,14]. In addition, urinary nucleosides also have been used to monitor progress of disease and response to therapy [4,[15][16][17][18].…”

Prospective study of urinary excretion of 7‐methylguanine and the risk of lung cancer: Effect modification by mu class glutathione‐S‐transferases

“…8 This may warrant further study of m 7 Gua as a product of repair of methylation damage to DNA, although m 7 Gua is also a metabolite from RNA. [28][29][30] The contribution from each of these pathways is unknown and more knowledge is required for the use of m 7 Gua as biomarker. In this context associations with well established biomarkers of exposure to TSNA, such as NNK, would be interesting.…”

“…26 The excretion has also been reported elevated in a small number of patients with colon cancer, 27 although not in patients with gastric cancer. 28 m 7 Gua is also a metabolite from RNA, [28][29][30] which affects interpretation as biomarker of exposure to methylating agents. On the other hand, the validity of a biomarker also includes the ability to predict outcome, e.g.…”

Age-dependence of urinary normal and modified nucleosides in childhood as determined by reversed-phase high-performance liquid chromatography

“…They are formed post-transcriptionally by various modification en-zymes, especially methyltransferases and ligases. The levels of the nucleosides in serum and urine reflect the turnover of RNA, in particular t-RNA [1][2][3][4]. Of clinical importance are mainly those modified nucleosides which are biochemical end products.…”