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Quadriceps miR-542-3p and 5p are elevated in COPD and reduce function by inhibiting ribosomal and protein synthesis

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Title: Quadriceps miR-542-3p and 5p are elevated in COPD and reduce function by inhibiting ribosomal and protein synthesis
Authors: Farre-Garros, R
Lee, J
Natanek, S
Connolly, M
Sayer, A
Patel, H
Cooper, C
Polkey, M
Kemp, P
Item Type: Journal Article
Abstract: Reduced physical performance reduces quality of life in patients with COPD. Impaired physical performance is, in part, a consequence of reduced muscle mass and function, which is accompanied by mitochondrial dysfunction. We recently showed that miR-542-3p and miR-542-5p were elevated in a small cohort of COPD patients and more markedly in critical care patients. In mice these miRNAs promoted mitochondrial dysfunction suggesting that they would affect physical performance in patients with COPD but we did not explore the association of these miRNAs with disease severity or physical performance further. We therefore quantified miR-542-3p/5p and mitochondrial rRNA expression in RNA extracted from quadriceps muscle of patients with COPD and determined their association with physical performance. As miR-542-3p inhibits ribosomal protein synthesis its ability to inhibit protein synthesis was also determined in vitro.Both miR-542-3p and -5p expression were elevated in patients with COPD (5-fold p<0.001) and the degree of elevation associated with impaired lung function (TLCO% and FEV1%) and physical performance (6-minute walk distance %). In COPD patients, the ratio of 12S rRNA to 16S rRNA was suppressed suggesting mitochondrial ribosomal stress and mitochondrial dysfunction and miR-542-3p/5p expression was inversely associated with mitochondrial gene expression and positively associated with p53 activity. miR-542-3p suppressed RPS23 expression and maximal protein synthesis in vitro. Our data show that miR-542-3p and -5p expression is elevated in COPD patients and may suppress physical performance at least in part by inhibiting mitochondrial and cytoplasmic ribosome synthesis and suppressing protein synthesis.
Issue Date: 24-Jan-2019
Date of Acceptance: 21-Jan-2019
URI: http://hdl.handle.net/10044/1/67191
DOI: https://dx.doi.org/10.1152/japplphysiol.00882.2018
ISSN: 8750-7587
Publisher: American Physiological Society
Journal / Book Title: Journal of Applied Physiology
Copyright Statement: © 2019, Journal of Applied Physiology.
Sponsor/Funder: Medical Research Council (MRC)
British Heart Foundation
Rosetrees Trust
Funder's Grant Number: 97159 (MRC ref G1001362)
FS/14/71/31038
A960
Keywords: COPD
microRNA
mitochondrial and cytoplasmic ribosomes
protein synthesis
06 Biological Sciences
11 Medical And Health Sciences
Physiology
Publication Status: Published online
Embargo Date: 2020-01-24
Online Publication Date: 2019-01-24
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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