This study develops a novel 3D human skeletal muscle organoid platform to study the immediate molecular effects of exercise-like contractions. The model uncovers rapid proteomic and transcriptomic re....

Reducing Ca2+ leak through mutant RYR1 prevents pathological heat production in skeletal muscle.

Accurate and reproducible tools to evaluate skeletal muscle contractility help to advance the field of physiology by defining skeletal muscle function in the context of skeletal muscle development, di...

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene resulting in dystrophin deficiency in skeletal/cardiac muscle and progressive loss of function. While the genetic causes of DMD...

Sica et al. show that the circadian clock in the brain controls daily rhythms in muscle stem cells. These rhythms affect stem cell metabolism and repair capacity, even in the absence of a local clock....

Background Dystrophin mRNA is produced from a very large genetic locus and transcription of a single mRNA requires approximately 16 h. This prolonged interval between initiation and completion results in unusual transcriptional behaviour: in skeletal muscle, myonuclei express dystrophin continuously and robustly, yet degrade mature transcripts shortly after completion. Consequently, most dystrophin mRNA is nascent, not mature. This implies expression is principally controlled post-transcriptionally, a mechanism that circumvents transcriptional delay, allowing rapid responses to change in demand. Dystrophin protein is however highly stable, with slow turnover: in healthy muscle, despite constant production of dystrophin mRNA, demand is low and the need for responsive expression is minimal. We reasoned this system instead exists to control dystrophin expression during rare periods of elevated but changing demand, such as during muscle development or repair, when newly formed fibres must establish sarcolemmal dystrophin rapidly. Methods We assessed dystrophin mRNA (both nascent and mature) and dystrophin protein in regenerating skeletal muscle following injury, using a combination of qPCR, immunofluorescence and in-situ hybridisation to determine timing and location of expression during the repair process. Results We reveal a complex program that suggests control at multiple levels: nascent transcription is detectable even prior to overt myoblast fusion, suggesting cells ‘pay in advance’ to minimise subsequent delay. During myotube differentiation and maturation, when sarcolemmal demands are high, initiation increases only modestly while mature transcript stability increases markedly to generate high numbers of mature dystrophin transcripts, a state that persists until repair is complete, when oversupply and degradation resumes. Conclusion Our data demonstrate that dystrophin mRNA is indeed chiefly controlled by turnover, not initiation: degradation consequently represents a potential therapeutic target for maximising efficacy of even modest dystrophin restoration.

Peng et al. show that DLL1-expressing muscle myoblasts not only regulate NOTCH signaling in neighbor cells but also send a retrograde signal to themselves via the DLL1 intracellular domain.

Therapeutic strategies for Duchenne muscular dystrophy (DMD) will likely require complementary approaches. One possibility is to explore genetic mo...

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder characterized by progressive muscle weakness and inflammation caused by mutat...

The extracellular matrix (ECM) niche regulates skeletal muscle stem cell (MuSC) behavior. Using transcriptomic data and 3D imaging, they show that quiescent MuSCs express unique ECM markers, including...

NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Request for Information on Draft Priorities for the Muscular Dystrophy Coordinating Committee's Action Plan NOT-NS-25-0...

An AAV-mediated gene therapy for myotonic dystrophy type 1 using a novel muscle-tropic capsid and promoter to express a DMPK-targeting miRNA effectively reduces DMPK expression and nuclear RNA foci, a...

Scaffolding protein ankyrin-B, implicated in cardiometabolic syndrome, enables mitochondrial fission and flexibility of nutrient utilization under energetic stress in skeletal muscle to support energy...

Background The development of functional muscles in Drosophila melanogaster relies on precise spatial and temporal transcriptional control, orchestrated by complex gene regulatory networks. Central to...

This study shows that two distinct progenitor populations build embryonic muscle in birds—one forms primary fibers via Wnt signaling, the other gives rise to secondary fibers and satellite cells—and t...

Background Pathogenic variants in RYR1 cause a spectrum of rare congenital myopathies associated with intracellular calcium dysregulation. Glutathione redox imbalance has been reported in several Ryr1...

With aging, somatic mutations accumulate in cellular DNA; however, whether they drive age-related functional decline is incompletely understood. Here the authors show that these mutations can weaken m...

Background Duchenne muscular dystrophy (DMD) leads to dilated cardiomyopathy and heart failure during teenage years or young adulthood. Eteplirsen promotes dyst...