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

Quadriceps miR-542-3p and 5p are elevated in COPD and reduce function by inhibiting ribosomal and protein
Quadriceps miR-542-3p and 5p are elevated in COPD and reduce function by inhibiting ribosomal and protein
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.
8750-7587
Farre-Garros, R.
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Lee, J.-Y.
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Natanek, S.A.
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Connolly, M.
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Aihie Sayer, A.
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb
Patel, H.P.
e1c0826f-d14e-49f3-8049-5b945d185523
Cooper, C.
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Polkey, M.I.
b6180039-7773-41c1-b9f3-f548d060ba89
Kemp, P.R.
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Farre-Garros, R.
6630dd51-4f51-450f-8e51-3304480095c2
Lee, J.-Y.
c59195e4-4d68-4cec-8261-87be0eb5260d
Natanek, S.A.
7db33b9b-ed00-4870-9866-aac627232c60
Connolly, M.
45e4ab7f-4331-4794-87cf-632b64dd236d
Aihie Sayer, A.
fb4c2053-6d51-4fc1-9489-c3cb431b0ffb
Patel, H.P.
e1c0826f-d14e-49f3-8049-5b945d185523
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Polkey, M.I.
b6180039-7773-41c1-b9f3-f548d060ba89
Kemp, P.R.
8482e7af-8844-4d6b-9768-71888a78b884

Farre-Garros, R., Lee, J.-Y., Natanek, S.A., Connolly, M., Aihie Sayer, A., Patel, H.P., Cooper, C., Polkey, M.I. and Kemp, P.R. (2019) Quadriceps miR-542-3p and 5p are elevated in COPD and reduce function by inhibiting ribosomal and protein. Journal of Applied Physiology. (doi:10.1152/japplphysiol.00882.2018).

Record type: 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.

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miR-542 in COPD CLEAN - Accepted Manuscript
Restricted to Repository staff only until 24 January 2020.
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542 COPD rev
Restricted to Repository staff only until 24 January 2020.
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More information

Accepted/In Press date: 21 January 2019
e-pub ahead of print date: 24 January 2019

Identifiers

Local EPrints ID: 427998
URI: https://eprints.soton.ac.uk/id/eprint/427998
ISSN: 8750-7587
PURE UUID: 48953d6c-81c7-48cc-968c-127ffa940ad5
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 06 Feb 2019 17:30
Last modified: 11 Apr 2019 00:37

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