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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2021
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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) |
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Medicine R Science Q Agnieszka Piasecka Michał Sekrecki Michał Wojciech Szcześniak Krzysztof Sobczak MEF2C shapes the microtranscriptome during differentiation of skeletal muscles |
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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 |
_version_ |
1718394668795822080 |