Amazing stuff! There is still so much to discover in the human genome!
"... A team at Yale University has now claimed a breakthrough with a technology they liken to "spray paint" for cells, which they've now demonstrated by mapping previously unknown [micro] proteins for the first time. ...
In search of the unknown elements that remained, some scientists began using cutting-edge techniques to identify proteins in biological samples that measured less than 100 amino acid units. ...
Despite these advances, there remains many more microproteins to discover. Based on preliminary research, scientists ... suspect these may be connected to human disease, helping melanoma and other types of cancers evade current treatments, for example. ...
One of the more promising techniques for discovering microproteins today is called proximity biotinylation, which is based on the premise that by fixing enzymes to certain proteins, other proteins they interact with can be revealed by affixing a chemical tag for easy identification. There are a few variations of this technology, and Yale scientists including Slavoff have been working with a form they call MicroID.
In search of the unknown elements that remained, some scientists began using cutting-edge techniques to identify proteins in biological samples that measured less than 100 amino acid units. ...
Despite these advances, there remains many more microproteins to discover. Based on preliminary research, scientists ... suspect these may be connected to human disease, helping melanoma and other types of cancers evade current treatments, for example. ...
One of the more promising techniques for discovering microproteins today is called proximity biotinylation, which is based on the premise that by fixing enzymes to certain proteins, other proteins they interact with can be revealed by affixing a chemical tag for easy identification. There are a few variations of this technology, and Yale scientists including Slavoff have been working with a form they call MicroID.
“Our technique is like spray painting various areas of a cell with a tag that allowed us to ‘grab’ and identify all of the microproteins in that cellular region,”...
The researchers have now used this technique to map previously unannotated microproteins in live cells for the first time. ..."
"Many of the thousands of proteins that help our cells grow and function remain undiscovered, especially the tiniest ones that occupy what some Yale scientists are calling the “dark matter” of our genome. ..."
From the abstract:
"Proteogenomic identification of translated small open reading frames has revealed thousands of previously unannotated, largely uncharacterized microproteins, or polypeptides of less than 100 amino acids, and alternative proteins (alt-proteins) that are co-encoded with canonical proteins and are often larger. The subcellular localizations of microproteins and alt-proteins are generally unknown but can have significant implications for their functions. Proximity biotinylation is an attractive approach to define the protein composition of subcellular compartments in cells and in animals. Here, we developed a high-throughput technology to map unannotated microproteins and alt-proteins to subcellular localizations by proximity biotinylation with TurboID (MicroID). More than 150 microproteins and alt-proteins are associated with subnuclear organelles. One alt-protein, alt-LAMA3, localizes to the nucleolus and functions in pre-rRNA transcription. We applied MicroID in a mouse model, validating expression of a conserved nuclear microprotein, and establishing MicroID for discovery of microproteins and alt-proteins in vivo."
Mapping subcellular localizations of unannotated microproteins and alternative proteins with MicroID (no public access)
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