The long noncoding RNA <i>Meg3</i> regulates myoblast plasticity and muscle regeneration through epithelial-mesenchymal transition

Dill, Tiffany L.; Carroll, Alina; Pinheiro, Amanda; Gao, Jiachen; Naya, Francisco J.

doi:10.1242/dev.194027

Cited by 18 publications

(15 citation statements)

References 70 publications

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“…Meg3 is an endogenously polyadenylated lncRNA which has been shown to regulate myoblast differentiation in vitro. We found Meg3 expression to be confined to the injury locus at 5dpi, when myoblast differentiation and myocyte fusion occurs 5,13 . Gm10076 , a transcript with a biotype annotation conflict (Ensembl: lncRNA; NCBI: pseudogene) and no known function, was highly and specifically expressed within the injury locus 2dpi.…”

Section: Resultsmentioning

confidence: 75%

In situ polyadenylation enables spatial mapping of the total transcriptome

McKellar

Mantri

Hinchman

et al. 2022

Preprint

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Spatial transcriptomics reveals the spatial context of gene expression, but current methods are limited to assaying polyadenylated (A-tailed) RNA transcripts. Here we demonstrate that enzymatic in situ polyadenylation of RNA enables detection of the full spectrum of RNAs, expanding the scope of sequencing-based spatial transcriptomics to the total transcriptome. We apply this Spatial Total RNA-Sequencing (STRS) approach to study skeletal muscle regeneration and viral-induced myocarditis. Our analyses reveal the spatial patterns of noncoding RNA expression with near-cellular resolution, identify spatially defined expression of noncoding transcripts in skeletal muscle regeneration, and highlight host transcriptional responses associated with local viral RNA abundance. In situ polyadenylation requires the addition of only a single step to a widely used protocol for spatial RNA-sequencing, and thus could be broadly and quickly adopted. Spatial RNA-sequencing of the total transcriptome will enable new insights into spatial gene regulation and biology.

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Section: Resultsmentioning

confidence: 75%

In situ polyadenylation enables spatial mapping of the total transcriptome

McKellar

Mantri

Hinchman

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Meg3 is an endogenously polyadenylated lncRNA that has been shown to regulate myoblast differentiation in vitro. We found Meg3 expression to be confined to the injury locus at 5 dpi, when myoblast differentiation and myocyte fusion occurs 5,16 . Gm10076, a transcript with a biotype annotation conflict (Ensembl: lncRNA; NCBI: pseudogene) and no known function, was highly and specifically expressed within the injury locus at 2 dpi.…”

Section: Strs Reveals Spatial Gene Regulation In Muscle Regenerationmentioning

confidence: 74%

Spatial mapping of the total transcriptome by in situ polyadenylation

et al. 2022

View full text Add to dashboard Cite

Spatial transcriptomics reveals the spatial context of gene expression, but current methods are limited to assaying polyadenylated (A-tailed) RNA transcripts. Here we demonstrate that enzymatic in situ polyadenylation of RNA enables detection of the full spectrum of RNAs, expanding the scope of sequencing-based spatial transcriptomics to the total transcriptome. We demonstrate that our spatial total RNA-sequencing (STRS) approach captures coding RNAs, noncoding RNAs and viral RNAs. We apply STRS to study skeletal muscle regeneration and viral-induced myocarditis. Our analyses reveal the spatial patterns of noncoding RNA expression with near-cellular resolution, identify spatially defined expression of noncoding transcripts in skeletal muscle regeneration and highlight host transcriptional responses associated with local viral RNA abundance. STRS requires adding only one step to the widely used Visium spatial total RNA-sequencing protocol from 10x Genomics, and thus could be easily adopted to enable new insights into spatial gene regulation and biology.

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“…Of note, other noncoding RNA species of the Dlk1-Dio3 locus (in addition to the DD-miRNAs) may participate in the regenerative process in the dystrophic muscle. In particular, the MEG3 transcript, which is up-regulated in DMD (Fig S3D and F), was shown recently to modulate epithelial to mesenchymal transition and the TGF-β pathway in the regenerating muscle (Dill et al, 2021).…”

Section: The Dd-mirna Cluster Regulates Mitochondrial Oxphos In the D...mentioning

confidence: 83%

Dlk1-Dio3 cluster miRNAs regulate mitochondrial functions in the dystrophic muscle in Duchenne muscular dystrophy

et al. 2022

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Duchenne muscular dystrophy (DMD) is a severe muscle disease caused by impaired expression of dystrophin. Whereas mitochondrial dysfunction is thought to play an important role in DMD, the mechanism of this dysfunction remains to be clarified. Here we demonstrate that in DMD and other muscular dystrophies, a large number of Dlk1-Dio3 clustered miRNAs (DD-miRNAs) are coordinately up-regulated in regenerating myofibers and in the serum. To characterize the biological effect of this dysregulation, 14 DD-miRNAs were simultaneously overexpressed in vivo in mouse muscle. Transcriptomic analysis revealed highly similar changes between the muscle ectopically overexpressing 14 DD-miRNAs and the mdx diaphragm, with naturally up-regulated DD-miRNAs. Among the commonly dysregulated pathway we found repressed mitochondrial metabolism, and oxidative phosphorylation (OxPhos) in particular. Knocking down the DD-miRNAs in iPS-derived skeletal myotubes resulted in increased OxPhos activities. The data suggest that (1) DD-miRNAs are important mediators of dystrophic changes in DMD muscle, (2) mitochondrial metabolism and OxPhos in particular are targeted in DMD by coordinately up-regulated DD-miRNAs. These findings provide insight into the mechanism of mitochondrial dysfunction in muscular dystrophy.

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The long noncoding RNA Meg3 regulates myoblast plasticity and muscle regeneration through epithelial-mesenchymal transition

Cited by 18 publications

References 70 publications

In situ polyadenylation enables spatial mapping of the total transcriptome

In situ polyadenylation enables spatial mapping of the total transcriptome

Spatial mapping of the total transcriptome by in situ polyadenylation

Dlk1-Dio3 cluster miRNAs regulate mitochondrial functions in the dystrophic muscle in Duchenne muscular dystrophy

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