New York, May 4 A new study has provided crucial insight into how a genetic element that has come to make up a large part of human DNA can successfully invade the nucleus to copy itself.
Viruses are known to use the genetic machinery of the human cells they invade to make copies of themselves.
As part of the process, viruses leave behind remnants throughout the genetic material (genomes) of humans.
The virus-like insertions, called “transposable elements,” are snippets of genetic material even simpler than viruses that also use host cell machinery to replicate, according to the study published in the journal Science Advances.
Nearly all these inserted elements have been silenced by our cells’ defence mechanisms over time, but a few, nicknamed “jumping genes,” can still move around the human genome like viruses.
Just one, called long interspersed nuclear element 1 (LINE-1), can still move by itself.
According to Liam J Holt, associate professor in the Department of Biochemistry and Molecular Pharmacology, and the Institute for Systems Genetics, at NYU Grossman School of Medicine, these “findings on the precise mechanisms behind LINE-1 insertion lay the foundations for the design of future therapies to prevent LINE-1 replication.”
To copy itself, however, LINE-1 must enter each cell’s nucleus, the inner barrier that houses DNA.
Led by researchers at NYU Langone Health and the Munich Gene Center at Ludwig-Maximilians-Universitat (LMU) Munchen in Germany, the study revealed that LINE-1 binds to cellular DNA during the brief periods when nuclei break open as cells continually divide in two, creating replacements to keep tissues viable as we age.
The research team found that LINE-1 RNA takes advantage of these moments, assembling into clusters with one of the two proteins it encodes, ORF1p, to hold tightly to DNA until the nucleus reforms after cell division.
“Moving forward, we will be looking to see if other condensates undergo functional changes as the ratios between their components change,” said Dr Holt.
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