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In 2014, as I started my doctoral work at the lab of Alan Saghatelian at the Salk Institute for Biological Studies in La Jolla, California, the idea that there were tiny proteins in our cells that had long been overlooked by researchers was gaining traction. Researchers had recently recognized that the genome contained genes that were so small that they had been missed by traditional genome annotation methods, and targeted searching for protein-coding snippets of DNA had suggested there may be many thousands of so-called microproteins hard at work in our cells.
Before I joined the lab, Saghatelian’s group had developed a new approach to validate the existence of some 400 microproteins across multiple human cell lines and tissues. Other labs were similarly confirming the existence of these predicted peptides, pointing to the ubiquitous nature of microproteins. But what were they doing?
The functions ...