Despite how much we know about the human genome, there are still
blind spots in the genome discovery algorithms. Using a technique that has
revealed more than 400 new proteins too tiny to be found by other means,
Yale researchers have helped identify a novel, functional
"microprotein" encoded in the human genome.
One of those microproteins, called NoBody, is a molecular
workhorse involved in sweeping out unneeded genetic material inside
cells. Its discovery may signal the existence of additional
microproteins involved in a host of key biological mechanisms and
diseases, the researchers said.
‘The discovery of microprotein 'NoBody' may signal the existence of additional microproteins involved in a host of key biological mechanisms and diseases.’
"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," said Sarah Slavoff,
co-senior author of a study published Dec. 5 in the journal Nature Chemical Biology
Slavoff is an assistant professor of chemistry and of molecular
biophysics and biochemistry at Yale. She is a member of the Chemical
Biology Institute at Yale's West Campus.
The study's first author is Nadia D'Lima, a researcher in
Slavoff's lab. Alan Saghatelian of the Salk Institute for Biological
Studies is the study's other co-senior author.
Saghatelian said, "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."
In previous work, the researchers began their search for
microproteins by examining myeloid leukemia cells and removing the
larger proteins. They used an analytical chemistry technique, liquid
chromatography-mass spectroscopy proteomics, to find the amino acid
sequences of every remaining protein.
Next, the researchers developed a computational method to build a
database of all possible microproteins in the sample. From this
database, Slavoff and her colleagues found more than 400 new
The study focused on a microprotein called NoBody, which stands
for non-annotated P-body dissociating polypeptide. The researchers found
that NoBody is a key ingredient in cells for recycling mRNA - genetic
blueprints for producing proteins - after those proteins have been
Slavoff said the finding hints that microproteins may play
important roles in many biological processes, as well as disease. There
are many neurological diseases, for example, that feature groupings of