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MiR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

ABSTRACT: miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

PROVIDER: PRJNA550529 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9593230.fastq.gz	Fastqsanger.gz
	SRR9593231.fastq.gz	Fastqsanger.gz
	SRR9593232.fastq.gz	Fastqsanger.gz
	SRR9593233.fastq.gz	Fastqsanger.gz
	SRR9593224.fastq.gz	Fastqsanger.gz

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miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro [miRNA-Seq]

Project description:miR-206, miR-1a-1 and miR-1a-2, foundational members of the myomir family, promote skeletal muscle differentiation and have complete identity in the seed sequence, suggesting functional redundancy. To test if the essential role of these three microRNAs in skeletal myogenesis was masked by redundant function of at least one of the three miRNA left in the cells in previous reports, we generated triple KO (tKO) C2C12 cells by CRISPR/Cas9 (in vitro) and triple KO mice (in vivo model). tKO myoblasts differentiate, producing similar levels of promyogenic mRNAs and normal fusion index. RNAseq analysis confirms tKO clones differentiate but also reveals decrease in mRNA levels of genes related to mitochondrial oxidative phosphorylation. Dimished mitochondria function in tKO cells was confirmed using Seahorse assay. The targets of miR-206/-1a are specifically upregulated during differentiation of tKO myoblasts, when the microRNAs are normally induced, confirming the complete loss of the three microRNA genes. Although we observe partial embryonic lethality of tKO mice, the live mice grow normally to adulthood, have the same size of skeletal muscles as control animals, but perform worse on physical activity tests, which may be partially explained by smaller skeletal muscle fiber diameters. Thus these three myomiRs are not essential for skeletal muscle differentiation but are required for optimal differentiation and provide a clear example of the microRNAs not being a switch but a modulator of differentiation.

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miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro [RNA-Seq]

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miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro [RNA-Seq]

Project description:miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro [RNA-Seq]

| PRJNA550533 | ENA

miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro [miRNA-Seq]

Project description:miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro [miRNA-Seq]

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miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro.

Project description:miR-206, miR-1a-1, and miR-1a-2 are induced during differentiation of skeletal myoblasts and promote myogenesis in vitro. miR-206 is required for skeletal muscle regeneration in vivo. Although this miRNA family is hypothesized to play an essential role in differentiation, a triple knock-out (tKO) of the three genes has not been done to test this hypothesis. We report that tKO C2C12 myoblasts generated using CRISPR/Cas9 method differentiate despite the expected derepression of the miRNA targets. Surprisingly, their mitochondrial function is diminished. tKO mice demonstrate partial embryonic lethality, most likely due to the role of miR-1a in cardiac muscle differentiation. Two tKO mice survive and grow normally to adulthood with smaller myofiber diameter, diminished physical performance, and an increase in PAX7 positive satellite cells. Thus, unlike other miRNAs important in other differentiation pathways, the miR-206 family is not absolutely essential for myogenesis and is instead a modulator of optimal differentiation of skeletal myoblasts.

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miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-15 | GSE133262 | GEO

miR-206 modulates the pathogenesis of muscular dystrophy of mdx mice

Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy. total RNA obtained from TA muscle of mdx and 3 miR-206 KO; mdx mice at 3 months of age.

2012-04-30 | E-GEOD-36077 | biostudies-arrayexpress

miR-206 modulates the pathogenesis of muscular dystrophy of mdx mice

2012-05-01 | GSE36077 | GEO