Scientists Uncover How LINE-1 Genetic Element Inserts Itself into Human DNA

Scientists Uncover How LINE-1 Genetic Element Inserts Itself into Human DNA

New research reveals how a “jumping gene” called LINE-1 sneaks into human DNA during cell division, explaining its role in disease and evolution.

At a Glance

  • Scientists have discovered that LINE-1, a mobile genetic element making up 20 percent of the human genome, copies itself by exploiting a vulnerable phase during cell division.
  • During this period, LINE-1 RNA clusters with the ORF1p protein to form condensates that help it insert into DNA while the nuclear barrier is temporarily broken.
  • The study found that LINE-1’s ability to jump depends on accumulating enough ORF1p protein to wrap around its RNA and create attachment points to the genome.
  • This mechanism allows LINE-1 to bypass normal cellular defenses and contributes to harmful effects like cancer, aging, and neurological disorders.
  • Understanding this process could lead to new therapies to prevent LINE-1 from disrupting important genes and triggering disease.

Scientists have made an important discovery about the behavior of a virus-like genetic element in our DNA called LINE-1. LINE-1 is a type of retrotransposon, which can “jump” around our genome by copying itself from RNA back into DNA. This ability allows it to make up about 20% of the human genome. While this jumping process helps drive evolution, it can also lead to diseases like cancer, neurological disorders, and aging if it inserts itself into important genes or triggers immune responses.

Model illustrating the formation of ORF1p-RNP complexes (condensates) and their role in DNA recognition during LINE-1 retrotransposition. ORF1p trimers and higher-order structures preferentially bind RNA, facilitating LINE-1’s integration into the genome. (Zernia et al., 2025)

In a new study published in Science Advances, researchers uncovered how LINE-1 manages to copy itself in human cells. To complete its copying process, LINE-1 must enter the cell’s nucleus, the central part of the cell where DNA is kept. The study shows that LINE-1 takes advantage of a brief period during cell division when the nucleus temporarily breaks open. During this time, LINE-1 RNA forms clusters with a protein called ORF1p, which helps LINE-1 bind to DNA, allowing it to insert itself into the genome.

The team from NYU Langone Health and Ludwig-Maximilians-Universität in Germany discovered that these clusters, called condensates, only work when enough ORF1p protein has built up. When ORF1p accumulates, it wraps around LINE-1 RNA, creating more sites to attach to the DNA. This is crucial for LINE-1’s ability to jump to new spots in the genome, especially during cell division. The process also helps LINE-1 avoid the cell’s defenses, which usually try to block large particles from entering the nucleus.

This discovery sheds new light on LINE-1’s behavior and could lead to new ways to stop it from causing damage in the body. Understanding how LINE-1 manages to insert itself into DNA could help develop therapies to prevent its harmful effects in the future. The research also opens the door to studying other genetic elements that might use similar strategies to affect our cells.


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