The Long Interspersed Element-1 (LINE-1) retrotransposon is an ‘ancient genetic parasite’ that has written around one third of the human genome through a ‘copy-and-paste’ mechanism and serves as an active source of genetic diversity and human disease.
The LINE-1 retrotransposon, one of the most common elements in human DNA, is a major part of the ‘dark genome,’ the poorly understood genetic material that doesn’t provide blueprints for any of the proteins that human bodies use.
Usually dormant in healthy cells, in disease, LINE-1 can break free and make proteins, including one called the LINE-1 ORF2 protein (LINE-1 ORF2p) that attempts to add new mutation-causing copies of LINE-1 back into our DNA.
Increased activity of the LINE-1 elements appears to be a common driver of autoimmunity, cancer, and other diseases.
Detailed knowledge of LINE-1, along with LINE-1 RNA and LINE-1 ORF2p, may enable the discovery or creation of drugs that bind to one or more of these molecules and stop them from damaging the body.
“Retrotransposons are often referred to as ‘jumping genes’ that insert themselves into our chromosomes with a copy-and-paste mechanism,” said University of Alberta’s Professor Matthias Götte.
“We discovered the essential steps in this process, which could then lead us to ways to inhibit the enzyme and eventually treat those diseases.”
The team was able to capture the first high-resolution images of LINE-1 ORF2p and reveal its structural details.
“As the paper explains, these analyses reveal the intricate workings of the molecular machine that has written nearly half of the human genome,” said Rutgers University’s Professor Eddy Arnold.
“The healthy body has mechanisms to repress these, but in disease states like cancers, these systems do not work properly.”
“Through this amazing team effort, we now have a detailed understanding of how LINE-1 ORF2p works,…
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