Muscle fix breakthrough
Researchers in the United States have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle.
Scientists at Sanford Burnham Prebys Medical Research Institute in La Jolla, California, were backed by the European Research Council, amongst others, and have outlined the essential role of a TBP-containing TFIID-protein complex in activating genes that regenerate muscle tissue. It shows that an alternative protein called TBP2 is not involved in this task in adult muscles.
The discovery resolves deep rooted conflicting data and is set to help streamline efforts towards boosting stem cell mediated muscle regeneration. Such strategies could treat muscle degenerative diseases such as muscular dystrophies, and those associated with ageing and cancer.
Commenting, Barbora Malecova, a postdoctoral fellow in the laboratory of Pier Lorenzo Puri and first author of the article, said: “Our discovery clarifies the identity of the ‘molecular switches’ that control the activation of muscle genes in muscle stem cells (MuSCs).
“Understanding what drives muscle gene expression gives us insights into molecular targets for regenerative medicine-based interventions (drugs) to treat muscle degenerative disorders.
“Previous reports had led researchers to believe that a transcription factor called TRF3 (also called TBP2) was absolutely required to activate muscle genes. Our new study shows that it’s actually a closely related complex called TFIID-TPB that’s key to regenerating muscle. In fact, we show that the TBP2 protein is not even expressed in muscle cells.”
MuSCs are adult stem cells present in skeletal muscle tissue that become activated in response to muscle injury to regenerate damaged muscle. In healthy skeletal muscle, MuSCs promote self-healing to repair muscle from normal wear and tear.
However, in disease conditions like muscular dystrophies, genetic mutations lead to the loss of key structural proteins of muscle cells, which results in cell dysfunction. Cells with these mutations can’t sustain the chronic regeneration pressure imposed by the disease, eventually resulting in progressive muscle weakness and death.
The research was published in the journal eLife.
