MEF2C shapes the microtranscriptome during differentiation of skeletal muscles

Abstract Myocyte enhancer factor 2C (MEF2C) is a transcription factor that regulates heart and skeletal muscle differentiation and growth. Several protein-encoding genes were identified as targets of this factor; however, little is known about its contribution to the microtranscriptome composition a...

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Autores principales: Agnieszka Piasecka, Michał Sekrecki, Michał Wojciech Szcześniak, Krzysztof Sobczak
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:fb929136498a4e399644d825635f831a2021-12-02T12:09:26ZMEF2C shapes the microtranscriptome during differentiation of skeletal muscles10.1038/s41598-021-82706-22045-2322https://doaj.org/article/fb929136498a4e399644d825635f831a2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82706-2https://doaj.org/toc/2045-2322Abstract Myocyte enhancer factor 2C (MEF2C) is a transcription factor that regulates heart and skeletal muscle differentiation and growth. Several protein-encoding genes were identified as targets of this factor; however, little is known about its contribution to the microtranscriptome composition and dynamics in myogenic programs. In this report, we aimed to address this question. Deep sequencing of small RNAs of human muscle cells revealed a set of microRNAs (miRNAs), including several muscle-specific miRNAs, that are sensitive to MEF2C depletion. As expected, in cells with knockdown of MEF2C, we found mostly downregulated miRNAs; nevertheless, as much as one-third of altered miRNAs were upregulated. The majority of these changes are driven by transcription efficiency. Moreover, we found that MEF2C affects nontemplated 3′-end nucleotide addition of miRNAs, mainly oligouridylation. The rate of these modifications is associated with the level of TUT4 which mediates RNA 3′-uridylation. Finally, we found that a quarter of miRNAs which significantly changed upon differentiation of human skeletal myoblasts is inversely altered in MEF2C deficient cells. We concluded that MEF2C is an essential factor regulating both the quantity and quality of the microtranscriptome, leaving an imprint on the stability and perhaps specificity of many miRNAs during the differentiation of muscle cells.Agnieszka PiaseckaMichał SekreckiMichał Wojciech SzcześniakKrzysztof SobczakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Agnieszka Piasecka
Michał Sekrecki
Michał Wojciech Szcześniak
Krzysztof Sobczak
MEF2C shapes the microtranscriptome during differentiation of skeletal muscles
description Abstract Myocyte enhancer factor 2C (MEF2C) is a transcription factor that regulates heart and skeletal muscle differentiation and growth. Several protein-encoding genes were identified as targets of this factor; however, little is known about its contribution to the microtranscriptome composition and dynamics in myogenic programs. In this report, we aimed to address this question. Deep sequencing of small RNAs of human muscle cells revealed a set of microRNAs (miRNAs), including several muscle-specific miRNAs, that are sensitive to MEF2C depletion. As expected, in cells with knockdown of MEF2C, we found mostly downregulated miRNAs; nevertheless, as much as one-third of altered miRNAs were upregulated. The majority of these changes are driven by transcription efficiency. Moreover, we found that MEF2C affects nontemplated 3′-end nucleotide addition of miRNAs, mainly oligouridylation. The rate of these modifications is associated with the level of TUT4 which mediates RNA 3′-uridylation. Finally, we found that a quarter of miRNAs which significantly changed upon differentiation of human skeletal myoblasts is inversely altered in MEF2C deficient cells. We concluded that MEF2C is an essential factor regulating both the quantity and quality of the microtranscriptome, leaving an imprint on the stability and perhaps specificity of many miRNAs during the differentiation of muscle cells.
format article
author Agnieszka Piasecka
Michał Sekrecki
Michał Wojciech Szcześniak
Krzysztof Sobczak
author_facet Agnieszka Piasecka
Michał Sekrecki
Michał Wojciech Szcześniak
Krzysztof Sobczak
author_sort Agnieszka Piasecka
title MEF2C shapes the microtranscriptome during differentiation of skeletal muscles
title_short MEF2C shapes the microtranscriptome during differentiation of skeletal muscles
title_full MEF2C shapes the microtranscriptome during differentiation of skeletal muscles
title_fullStr MEF2C shapes the microtranscriptome during differentiation of skeletal muscles
title_full_unstemmed MEF2C shapes the microtranscriptome during differentiation of skeletal muscles
title_sort mef2c shapes the microtranscriptome during differentiation of skeletal muscles
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/fb929136498a4e399644d825635f831a
work_keys_str_mv AT agnieszkapiasecka mef2cshapesthemicrotranscriptomeduringdifferentiationofskeletalmuscles
AT michałsekrecki mef2cshapesthemicrotranscriptomeduringdifferentiationofskeletalmuscles
AT michałwojciechszczesniak mef2cshapesthemicrotranscriptomeduringdifferentiationofskeletalmuscles
AT krzysztofsobczak mef2cshapesthemicrotranscriptomeduringdifferentiationofskeletalmuscles
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