A team of researchers from the University of Maryland used microscopic roundworms (C. elegans) to study how dsRNA naturally enters cells and influences genetic changes across generations. Their findings identified multiple pathways that dsRNA can utilize to enter worm cells effectively. This discovery holds promise for improving drug delivery methods in humans.

The Role of SID-1 Protein

The study focused on a protein known as SID-1, which acts as a gatekeeper for dsRNA information transfer. The researchers discovered that SID-1 not only facilitates dsRNA entry but also plays a crucial role in regulating gene expression over many generations. When researches removed the SID-1 protein, they observed that the worms became more adept at passing genetic expression changes to their offspring. These changes persisted for over 100 generations, even after reintroducing SID-1.

“Interestingly, you can find proteins similar to SID-1 in other animals, including humans,” noted Jose. “Understanding SID-1 and its role could have significant implications for human medicine. If we can harness this protein’s ability to control RNA transfer between cells, it could help us develop better targeted treatments for human diseases and potentially influence the inheritance of certain diseases.”

Discovering the sdg-1 Gene

The team also uncovered a gene named sdg-1 that helps regulate ‘jumping genes’—DNA sequences that can move or copy themselves to different chromosome locations. While jumping genes can bring beneficial genetic variations, they also pose a risk by disrupting existing sequences, often leading to disease. The researchers found that sdg-1 is located within a jumping gene but produces proteins to control such movements, creating a regulatory loop that minimizes unwanted changes.

“It’s fascinating how these cellular mechanisms maintain this delicate balance, much like a thermostat keeping a house at a comfortable temperature,” Jose explained. “The system needs to be flexible enough to allow some jumping activity while preventing excessive movements that could harm the organism.”

Implications for Human Medicine

Jose believes that the team’s findings provide valuable insights into how animals, including humans, regulate genes and maintain stable gene expression across generations. Studying these mechanisms could pave the way for innovative treatments for hereditary diseases.

“We’re just scratching the surface,” Jose added. “What we discovered is just the beginning of understanding how external RNA can cause heritable changes that last for generations. This work will help scientists better design and deliver RNA-based medicines to patients effectively.”

Conclusion

The paper, “Intergenerational transport of double-stranded RNA in C. elegans can limit heritable epigenetic changes,” was published in eLife on February 4, 2025. In addition to senior author Antony Jose and lead author Nathan Shugarts (Ph.D. ’21, biological sciences), other UMD co-authors include biological sciences Ph.D. student Aishwarya Sathya, Andrew L. Yi (B.S. ’19, biological sciences; B.S. ’22, psychology), Winnie M. Chan (B.S. ’19, biological sciences; B.S. ’22, psychology), and Julia A. Marré (B.S. ’09, Ph.D. ’17, biological sciences).

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