Viruses utilize the genetic apparatus within human cells when they infect them for reproducing their own components. During this activity, these viruses deposit fragments across our genome’s structure. These viral leftovers, referred to as “transposable elements,” consist of segments of genetic code that are less complex compared to full-fledged viruses but similarly exploit cellular mechanisms for replication purposes.
Most of these added components have been muted by our cellular defenses over the years, yet some, dubbed “jumping genes,” continue to migrate within the human genome similar to viruses. Only one specific type, known as long interspersed nuclear element 1 (LINE-1), retains the ability to move independently.
Like the retrovirus HIV, the LINE-1 “retrotransposon” functions as a distinct entity. It initially creates a duplicate as an RNA strand—the genetic component that works alongside DNA—and subsequently transforms this RNA copy back into DNA at a different location within the genome.
This process enables retrotransposons to incorporate additional sequences into the human genome each time they relocate, accounting for the fact that approximately 500,000 LINE-1 repetitions currently make up a “remarkable” 20% of the human genome. Such repetitions fuel genomic evolution; however, they may also lead to neurological disorders, cancers, and aging when LINE-1 inserts itself haphazardly into crucial genes or provokes an immunological reaction akin to encountering a virus, resulting in inflammation.
To replicate itself, though, LINE-1 needs to penetrate each cell’s nucleus, which serves as the internal shield housing the DNA.
Now a new study,
published
online in the journal
Science Advances
reveals that LINE-1 attaches to cellular DNA during the short intervals when cell division causes nuclear membranes to temporarily split apart, helping to generate new cells needed for maintaining healthy tissue function as we age.
The study group discovered that LINE-1 RNA seizes these opportunities, forming complexes with one of the two proteins it produces, ORF1p, holding onto the DNA firmly until the nucleus regenerates following cell division.
The research, led by scientists from NYU Langone Health and the Munich Gene Center at Ludwig-Maximilians-Universität (LMU) München in Germany, found that LINE-1 binds to DNA exclusively when ORF1p—as it has the capability to attach to both RNA, DNA, and multiple self-copies known as multimers—aggregates into large structures referred to as condensates containing hundreds of units.
As the number of ORF1p particles increases, they progressively encapsulate the LINE-1 RNA, thereby increasing the availability of binding sites for the whole complex to adhere to the DNA.
“Our research offers vital understanding about how a genetic component that now constitutes a significant portion of human DNA manages to infiltrate the cell nucleus for replication purposes,” stated Liam J. Holt, Ph.D., who serves as an associate professor within the Department of Biochemistry and Molecular Pharmacology and the Institute for Systems Genetics at NYU Grossman School of Medicine.
These discoveries regarding the exact processes underlying LINE-1 insertion pave the way for developing potential treatments aimed at stopping LINE-1 replication.
The research indicates that the LINE-1 condensate functions as a transport mechanism to position its RNA near specific sequences (abundant in the DNA components adenine and thymine) on the DNA where the retrotransposon typically inserts itself, according to the study’s authors. Encapsulated within these condensates, LINE-1 appears to bypass the cell’s defenses—mechanisms that usually prevent large molecules from entering the nucleus during mitosis as protection against viral infections.
“LINE-1 condensates possess a distinctive trait where their capacity to bind with DNA appears exclusively when the proportion of ORF1 protein molecules relative to RNA within these condensates reaches an adequate level,” explained Dr. Holt. “In future research, our aim is to investigate whether alterations in component proportions trigger similar functionality shifts in other types of condensates.”
More information:
Sarah Zernia and colleagues found that LINE-1 ribonucleoprotein condensates attach to DNA, facilitating their passage into the nucleus during cell division.
Science Advances
(2025).
DOI: 10.1126/sciadv.adt9318
.
www.science.org/doi/10.1126/sciadv.adt9318
Furnished by NYU Langone Health
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