A new study suggests that our bodies produce more proteins than we thought
Northeastern research reveals that humans have a “highly abundant” number of stable proteins that are not all predicted by genetic code.
In 1968, the American biochemist and geneticist Marshall Nirenberg and his colleagues won the Nobel Prize in Physiology or Medicine for their work deciphering how an organism’s proteins are directly linked to its genetic code.
That discovery is considered to be a “fundamental pillar of molecular biology,” explained Nikolai Slavov, a distinguished professor of bioengineering. “It’s in every textbook from high school to college.”
For years, researchers have worked to build on Nirenberg’s work and to develop a deeper understanding of how proteins – which are responsible for muscle, skin and tissue maintenance — are formed.
Research from Slavov published in the scientific journal Nature adds a new chapter to the story. It reveals that humans contain a “highly abundant” number of stable proteins that are not all predicted by their genetic code, according to Slavov.
It wasn’t that Nirenberg’s finding was wrong, Slavov said. “We discovered that it is incomplete,” he explained.
Slavov’s and his colleagues’ findings could one day aid in the development of cancer treatments and in neurodegenerative conditions, like Alzheimer’s and Parkinson’s disease, which are characterized by protein dysfunction, he said.
The researchers spent years analyzing RNA, bedrock molecules in the production of proteins and DNA, bedrock molecules that carry genetic information, and other data from more than a thousand human samples. Much of the data was collected from the National Cancer Institute’s Health’s Clinical Proteomic Tumor Analysis Consortium, a national project designed to advance our understanding of cancer on a molecular level, and other public datasets.
The dataset included both healthy human tissues and samples from individuals with several different types of cancer, including renal, uterine, breast, prostate, and various forms of lung cancer.
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The researchers used mass spectrometry, a laboratory technique useful for identifying and breaking apart structures of molecules, and identified thousands of unexpected amino acid substitutions. Amino acids are the building blocks of proteins. Amino acid substitutions occur when one of those blocks is replaced for another.
These amino acids help produce previously unknown proteins through a process the researchers called “alternative RNA decoding,” Slavov said. This is the process of proteins being created from amino acid substitutions that “deviate from the genetic code.” This alternative RNA decoding process happens for a number of reasons, the researchers noted. One major explanation is stability. The researchers found that these types of proteins were both abundant in number and stable in design.
“The understanding has been that our protein sequences are particularly associated with DNA sequences,” he said. “What we found was that other processes contribute a lot to determine protein sequences.”
The researchers said they found many of these “new protein products” were more abundant in tissues around tumors when compared to other tissues. But Slavov cautioned that this doesn’t prove they were cancer-causing, but “it is very likely this reflects new cancer vulnerabilities,” he said.
Additionally, the proteins they observed have similar characteristics to proteins associated with Parkinson’s and Alzheimer’s, he said.
Shriri Tsour Meria, a Northeastern graduate who co-authored the paper as a doctoral student in Slavov’s lab, highlighted that these results challenge assumptions about protein production.
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“The fact that we were able to shake up this notion that every protein is encoded by the genetic code is probably not something a lot of people would pursue,” she said. “I think this is a lesson in persistence and not being afraid of pushing the envelope.”
Slavov said future, wider studies will need to be done to confirm his team’s findings and to establish more concrete links to cancer and other degenerative diseases. His team is already pursuing research on that front.
“It is a very fundamental observation that, if widely confirmed, is going to change textbooks and it’s going to have major implications for health and disease,” he said.
