Protein important for protein synthesis could also have role in murine regeneration

Written by Mike Gregg

Researchers from the University of Illinois (IL, US), have discovered that a protein more commonly known for its importance in protein synthesis has an unexpected role in influencing muscle regeneration and regrowth in cells. Their work, which is published in the Journal of Clinical Investigation, could lead to novel treatments for disorders that result in muscle loss.

Until recently, scientists have focused their research on the role of leucine tRNA-synthetases (LRS) in protein synthesis. However, novel research has identified that these proteins have a much larger role within the cell. 

“Previously, my lab and other labs discovered that one of such functions of LRS is that it can regulate cell growth. Our new study is the first report of its function in muscle regeneration,” explained Professor Jie Chen (University of Illinois, IL, US).

To establish the effect of LRS concentrations on muscle repair, Chen’s team used mammalian cell cultures and mice. They discovered mice with low levels of LRS recovered from muscle tissue injuries faster than their counterparts with normal LRS levels. They also found that protein synthesis in cells was unaffected by a 70% drop in LRS proteins in the cell.

“But lower levels do positively influence muscle regeneration. We saw that, seven days after injury, the repaired muscle cells are bigger when LRS is lower,” added Chen.

Chen and her researchers have since found the exact molecular mechanism by which LRS influences muscle regeneration. They clarified this by using a non-toxic inhibitor developed by their collaborators in South Korea that targets the mechanism. They found that when the inhibitor was introduced it blocked the effect of LRS on muscle cells without interfering with its role in protein synthesis.

“We showed that this inhibitor works both in mammalian cells and in mice,” stated Chen “Muscle repair occurred more rapidly — and the regenerated muscles were stronger — when the inhibitor was present.”

“We now understand that ‘protein moonlighting,’ where one protein does many different things in the cell, is the norm,” concluded Chen.

Going forward, Chen and her colleagues want to establish how older mice are affected by LRS.