Researchers may have discovered the hardest working microprotein in the human genome.
Yale researchers used a new technique to discover a bevy of proteins encoded in the human genome, including a workhorse microprotein called “Nobody,” which is involved in sweeping out unneeded generic material inside cells.
The discovery of Nobody may signal the existence of additional microproteins involved in a host of key biological mechanisms and diseases, according to Sarah Slavoff, co-senior author of the study and assistant professor of chemistry at Yale.
“The broadest significance of this work is that even in a well-studied biological process, a microprotein has been right there under our noses, undetected, all this time,” Slavoff said in a statement.
Nobody—which stands for non-annotated P-body dissociating polypeptide—is a key ingredient in cells for recycling mRNA—which are genetic blueprints for producing proteins—after those proteins have been created.
According to Slavoff, the finding hints that microproteins may play crucial roles in many biological processes. There are also many neurological diseases that feature groupings of proteins.
Along with Slavoff, who is a member of the Chemical Biology Institute at Yale’s West Campus, Nadia D’Lima, a researcher in Slavoff’s lab is the study’s first author and Alan Saghatelian of the Salk Institute for Biological Studies is the study’s other co-senior author.
Saghatelian explained the importance of the discovery.
“Despite how much we know about the human genome, there are still blind spots in the genome discovery algorithms,” he said in a statement. “You can sequence the whole human genome and never know a protein, like this one, was there because it’s too short and falls below the usual length requirement for gene assignment algorithms.”
The recent discovery comes on the heels of previous research where the scientists examined myeloid leukemia cells and removed the larger protein. They were able to use an analytical chemistry technique—liquid chromatography-mass spectroscopy proteomics—to find amino acid sequences of every remaining protein.
The researchers then developed a computational method to build a database of all possible microproteins in the sample, which led to the discovery of 400 new microproteins.
Additional authors of the study included Lauren Winkler of Yale, Jiao Ma and Qian Chu of the Salk Institute, Ken Loh of the Massachusetts Institute of Technology, Elizabeth Corpuz and Jens Lykke-Anderson of the University of California-San Diego, and Bogdan Budnik of Harvard.