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Here, we developed a novel stable isotope (D\n                    <jats:sub>2<\/jats:sub>\n                    O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells were incubated in D\n                    <jats:sub>2<\/jats:sub>\n                    O-enriched media and myotubes \u00b150 ng\/ml IGF-I. Second, rat quadriceps (untrained, n = 9; 7-wk interval-\u201clike\u201d training, n = 13) were collected after ~3-wk D\n                    <jats:sub>2<\/jats:sub>\n                    O (70 atom %) administration, with body-water enrichment monitored via blood sampling. Finally, 10 (23 \u00b1 1 yr) men consumed 150-ml D\n                    <jats:sub>2<\/jats:sub>\n                    O followed by 50 ml\/wk and undertook 6-wk resistance exercise (6 \u00d7 8 repetitions, 75% 1-repetition maximum 3\/wk) with body-water enrichment monitored by saliva sampling and muscle biopsies (for determination of RNA synthesis) at 0, 3, and 6 wk. Ribose mole percent excess (r-MPE) from purine nucleotides was analyzed via GC-MS\/MS. Proliferating C2C12 cell r-MPE exhibited a rise to plateau, whereas IGF-I increased myotube RNA from 76 \u00b1 3 to 123 \u00b1 3 ng\/\u03bcl and r-MPE by 0.39 \u00b1 0.1% (both P &lt; 0.01). After 3 wk, rat quadriceps r-MPE had increased to 0.25 \u00b1 0.01% ( P &lt; 0.01) and was greater with running exercise (0.36 \u00b1 0.02%; P &lt; 0.01). Human muscle r-MPE increased to 0.06 \u00b1 0.01 and 0.13 \u00b1 0.02% at 3\/6 wk, respectively, equating to synthesis rates of ~0.8%\/day, increasing with resistance exercise to 1.7 \u00b1 0.3%\/day ( P &lt; 0.01) and 1.2 \u00b1 0.1%\/day ( P &lt; 0.05) at 3\/6 wk, respectively. Therefore, we have developed and physiologically validated a novel technique to explore ribosomal biogenesis in a multimodal fashion.\n                  <\/jats:p>","DOI":"10.1152\/ajpendo.00157.2017","type":"journal-article","created":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T20:50:16Z","timestamp":1502830216000},"page":"E681-E689","source":"Crossref","is-referenced-by-count":30,"title":["A novel D\n                    <sub>2<\/sub>\n                    O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle"],"prefix":"10.1152","volume":"313","author":[{"given":"M. S.","family":"Brook","sequence":"first","affiliation":[{"name":"Medical Research Council-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. J.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Medical Research Council-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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E.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Medical Research Council-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. J.","family":"Szewczyk","sequence":"additional","affiliation":[{"name":"Medical Research Council-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Kainulainen","sequence":"additional","affiliation":[{"name":"Department of Biology of Physical Activity, University of Jyv\u00e4skyl\u00e4, Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Lensu","sequence":"additional","affiliation":[{"name":"Department of Biology of Physical Activity, University of Jyv\u00e4skyl\u00e4, Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. G.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. L.","family":"Britton","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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