Proteins: prime movers
Proteins are essential for life as we know it. If you day-dream, digest food, walk and run, or admire a painting, it is because you are expressing specific proteins for those functions. Appropriately derived from the Greek proteios, meaning "primary", they are the movers and shakers of our bodies, participating in practically every process within our cells.
Yet the life of the party, so to speak, can also bring the house crashing down – when a disease occurs within our body, it is because specific proteins become less active or fail to act all together.
Indeed, virtually all current drugs target proteins in order to restore normal protein functions within our bodies. That’s why it is crucial for researchers to understand what proteins we express, how they work, and how their activity is affected by disease.
Iconoclastic discovery: 83,000 proteins hidden in plain sight
A recent discovery by Université de Sherbrooke researcher Dr. Xavier Roucou is, however, shaking up the medical community by throwing into question our basic understanding of proteins.
Named one of the Top 10 Discoveries of the Year by the prestigious magazine Québec Science, Dr. Roucou and his team of investigators at the Université de Sherbrooke’s Centre de Recherche Clinique Étienne-Le Bel have discovered more than 80,000 proteins that were until now, invisible and thus unknown to science.
“Yet they were right there before our eyes the entire time,” says Dr. Roucou, who teased the staggering volume of new ‘alternate’ proteins into sight with doctoral student Benoît Vanderperre, by rigorously investigating the human genome using several bioinformatics tools to predict alternative protein coding sequences.
The scientific community is understandably perplexed since the discovery puts into question what has long been considered basic knowledge in biology. The observation is so iconoclastic that Dr. Roucou's team had a hard time getting its work published in some journals.
“Our findings are provocative,” admits Dr. Roucou. “In mammalians, only a few alternative proteins have been serendipitously discovered in the last ten years. And that is why I think many scientists are perplexed – how could we have missed so many proteins?”
Cells use mRNA as an intermediate support in producing the proteins they need. One tenet still persists about this mechanism: ribosomes produce a single protein for each mature mRNA, referred to as the reference protein, which plays a very specific role in the cell. Dr. Roucou's team discovered that there is not just one way to decode a mature mRNA.
“We can now confirm that this basic tenet is inexact,” explains Dr. Roucou. “Ribosomes can decode the information transmitted to them by mRNA in a variety of ways, leading to the production of many completely different alternative proteins.”
In short, from a single mature mRNA, Dr. Roucou has discovered that cells produce not one, but many distinct proteins, which necessarily involves many functions. According to the data they have collected, each messenger RNA codes 3.8 proteins on average, rather than one as was commonly understood thus far.
Discoveries around the corner
Dr. Roucou says that he has always been amazed by the complexity of life. “The study of the chemistry of life, or biochemistry, has therefore been a natural adventure for me,” he explains. “I became interested in health research because I want to contribute to improving the lives of people.”
His laboratory has had a long interest in neuronal degeneration, and much of his efforts are aimed at understanding molecular mechanisms responsible for the untimely demise of neurons in neurodegenerative diseases, such as Alzheimer's disease, spinocerebellar ataxia type 1 and Prion disease. “Identifying these mechanisms will open new therapeutic perspectives that are direly needed for these disorders,” he explains.
In addition to requiring biologists to revise their textbooks, alternative proteins could possibly help thwart diseases like cancer and degenerative diseases.
“This discovery is a turning point in my career and I am now focusing on the study of this parallel universe in the human genome,” says Dr. Roucou.
“This is going to be the biggest challenge yet in my career in health research.”