Microprotein important for maintaining human cell health discovered

Researchers from Yale University in New Haven, CT, and the Salk Institute in La Jolla, CA, describe how they found their new microprotein - which they name NoBody (non-annotated P-body dissociating polypeptide) - along with hundreds of others, in the journal Nature Chemical Biology.

Researchers developed new microprotein

They suggest that changes to NoBody levels inside cells could disrupt RNA recycling, which is an important cell-clearing process. The discovery could lead to new treatments that target RNA dysfunction. "The discovery of NoBody and its function in mRNA recycling suggests that at least some of the hundreds of other microproteins that we have found might also be functional, which is an exciting proposition," says Prof. Saghatelian.

By combining genomic sequencing and liquid chromatography-mass spectroscopy proteomics, the researchers developed a new microprotein detection strategy to look for tiny proteins that conventional genome sequencing would overlook.

They took the contents of cells from a commonly studied myeloid leukemia cell line and removed the larger proteins. Using the new strategy, they determined the amino acid sequences of every protein that was left.

To find out which genes coded for these proteins, the team developed a computational method to make a database containing every possible microprotein from all of a myeloid cell's mRNAs - which they sequenced using genomics techniques.

The researchers then used the custom database to search their new protein sequences for matches to real proteins and found over 400 new microproteins, including NoBody. When they studied NoBody more closely, the researchers found that it interacts with proteins that help regulate the recycling of mRNAs at points inside cells known as P-body granules. Clusters of mRNA and proteins that perform the first step in breaking down the mRNAs accumulate at these points.

Proteins are the workhorses of the cell. Their genetic blueprints are encoded in DNA and obediently carried to the cell's protein-making machinery by molecules called messenger RNA - dubbed mRNA. Since the completion of the Human Genome Project in 2003 - where scientists sequenced and mapped all of the genes for building Homo sapiens - we have learned a lot about proteins, their associated genes, and the RNA mechanisms that translate them.

 This image of human kidney cells shows NoBody (green), P-body markers (red), cell nuclei (blue), and NoBody interacting with P-bodies (yellow).
(Image credit: MIT/Yale University )

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