WASHINGTON — Researchers have discovered the “unpreviously” enormous amount of proteins in the muscle protein-rich cells of humans.
The finding raises new questions about the roles of muscle protein turnover and is potentially key to better understanding the mechanisms underlying muscle loss and muscle wasting, according to researchers from Brigham and Women’s Hospital in Boston.
It was only recently that researchers have been able to identify specific genes that control protein synthesis and breakdown, and how they interact with one another, said senior author Richard M. Cote, MD, MPH, a professor of genetics and cell biology at Boston University School of Medicine.
Now, researchers have identified proteins that are present in muscle cells that have previously only been found in skeletal muscle.
These proteins, known as protein-coding RNAs (PCRs), are a key part of the cellular machinery of muscle and play a crucial role in regulating the rate of protein synthesis, said Dr. Cotes.
This finding has the potential to provide insights into how muscle cell types are connected and the mechanisms by which protein breakdown occurs.
The findings, published online May 17 in the journal Cell Reports, could help explain why some types of muscle are more efficient at repairing damage than others, and could potentially help researchers design better and more efficient drugs to prevent and treat muscle damage, Dr. Mote said.
A study published earlier this year in Nature Biotechnology found that the majority of human muscle proteins were encoded by the same type of gene, which led to the idea that the same genetic code was controlling the same set of protein-protein interactions.
But the study was limited in its ability to identify the specific genes involved.
“The new study reveals that the genetic code of muscle proteins is a much more complex network of interacting genes than we thought,” said study senior author Muneo T. Ohnuma, PhD, a graduate student in Dr. David Cote’s lab.
“This allows us to look for a number of protein coding RNAs, some of which have previously been only found in human skeletal muscle, in human cells, and in muscle proteins from different types of animals.
We find a remarkable number of proteins from human muscle that are expressed at different rates in the same muscle cell type.
The molecular mechanisms by the end result are very surprising.”
The findings add to the body of evidence that proteins from one cell type are more likely to be expressed in another, and that this process is often linked to the protein’s activity in the cell, Drs.
Ohno and Cote said in a statement.
“These findings have important implications for understanding the roles and functions of various types of protein and how these proteins can be used to regulate various cellular processes,” Drs Ohno, Cote and colleagues wrote.
“It also opens up opportunities for using these insights to design more effective treatments for muscle diseases and muscle-wasting diseases, such as muscle wasting.”
Dr. Oh no longer holds the same title as the late Dr. Richard Mote, whose seminal paper on protein-based cellular biology was published in 2001.
Dr. Cotes group has published numerous studies that have shown that different proteins from the same cell type interact more strongly with one other, leading to higher levels of activity.
These interactions could also affect the function of proteins involved in muscle repair, and protein degradation, and cellular signaling.
For instance, proteins from a cell type that is more sensitive to oxidative stress, such a muscle, could be more responsive to inflammation or to damage to connective tissue, and would therefore be less effective at repairing muscle damage.
In addition, muscle-derived proteins, such the ones found in the human liver and pancreas, have been shown to play a role in muscle health.