The Dark Matter of the Human Proteome

Advances in the functional characterization of newly discovered microproteins hint at diverse roles in health and disease.

Written byAnnie Rathore
| 10 min read
Advances in the functional characterization of newly discovered microproteins hint at their diverse roles  in health and disease

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ABOVE: MODIFIED FROM © istock.com, erhui1979

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 ...

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