{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:24:03Z","timestamp":1789619043322,"version":"build-2803163510"},"reference-count":68,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T00:00:00Z","timestamp":1512604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000550","name":"British Geriatrics Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A loss of muscle mass occurs as a consequence of a range of chronic and acute diseases as well as in older age. This wasting results from an imbalance of protein synthesis and degradation with a reduction in synthesis and resistance to anabolic stimulation often reported features. Ribosomes are required for protein synthesis, so changes in the control of ribosome synthesis are potential contributors to muscle wasting. MicroRNAs (miRNAs) are known regulators of muscle phenotype and have been shown to modulate components of the protein synthetic pathway. One miRNA that is predicted to target a number of components of protein synthetic pathway is miR\u2010424\u20105p, which is elevated in the quadriceps of patients with chronic obstructive pulmonary disease (COPD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Targets of miR\u2010424\u20105p were identified by Argonaute2 pull down, and the effects of the miRNA on RNA and protein expression were determined by quantitative polymerase chain reaction and western blotting in muscle cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Protein synthesis was determined by puromycin incorporation\n                      <jats:italic>in vitro<\/jats:italic>\n                      . The miRNA was over\u2010expressed in the\n                      <jats:italic>tibialis anterior<\/jats:italic>\n                      muscle of mice by electroporation and the effects quantified. Finally, quadriceps expression of the miRNA was determined by quantitative polymerase chain reaction in patients with COPD and intensive care unit (ICU)\u2010acquired weakness and in patients undergoing aortic surgery as well as in individuals from the Hertfordshire Sarcopenia Study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pull\u2010down assays showed that miR\u2010424\u20105p bound to messenger RNAs encoding proteins associated with muscle protein synthesis. The most highly enriched messenger RNAs encoded proteins required for the Pol I RNA pre\u2010initiation complex required for ribosomal RNA (rRNA) transcription, (PolR1A and upstream binding transcription factor).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , miR\u2010424\u20105p reduced the expression of these RNAs, reduced rRNA levels, and inhibited protein synthesis. In mice, over\u2010expression of miR\u2010322 (rodent miR\u2010424 orthologue) caused fibre atrophy and reduced upstream binding transcription factor expression and rRNA levels. In humans, elevated miR\u2010424\u20105p associated with markers of disease severity in COPD (FEV\n                      <jats:sub>1<\/jats:sub>\n                      %), in patients undergoing aortic surgery (LVEF%), and in patients with ICU\u2010acquired weakness (days in ICU). In patients undergoing aortic surgery, preoperative miR\u2010424\u20105p expression in skeletal muscle was associated with muscle loss over the following 7\u00a0days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data suggest that miR\u2010424\u20105p regulates rRNA synthesis by inhibiting Pol I pre\u2010initiation complex formation. Increased miR\u2010424\u20105p expression in patients with conditions associated with muscle wasting is likely to contribute to the inhibition of protein synthesis and loss of muscle mass.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12266","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T06:58:47Z","timestamp":1512629927000},"page":"400-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["miR\u2010424\u20105p reduces ribosomal RNA and protein synthesis in muscle wasting"],"prefix":"10.1002","volume":"9","author":[{"given":"Martin","family":"Connolly","sequence":"first","affiliation":[{"name":"Molecular Medicine Section National Heart and Lung Institute, Imperial College London  South Kensington Campus London SW7\u00a02AZ 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