Researchers at Karolinska Institutet and Uppsala University have developed a powerful new technique to better understand how tiny molecules in our cells, called microRNAs, control which genes are turned on or off - a discovery that could improve how we study diseases from cancer to neurodevelopmental disorders.
MicroRNAs (miRNAs) are short strings of RNA that help regulate gene activity. Most of their effects come from a part known as the "seed" region, which allows them to latch onto messenger RNAs and block the production of certain proteins. But researchers have long suspected that other regions of the microRNA might also matter and until now, those effects were hard to isolate and measure.
Led by Dr. David Kosek and Dr. Emma R. Andersson from the Department of Cell and Molecular Biology the team used a clever molecular trick: they altered just two tiny spots in the miRNA specifically in miR-34a so it could no longer bind to parts of the target RNA. They then measured how this change affected gene expression in human cells.
The results were striking, while most genes still responded normally, a specific group of targets showed significantly reduced regulation confirming that this lesser-known "tail end" of the microRNA plays an important role in fine-tuning gene activity.
The method also showed that some types of structures or mismatches in the binding process are more disruptive than others, an insight that could help researchers design better microRNA-based diagnostics or therapies in the future.
The study, published in Nucleic Acids Research, opens the door to more precise exploration of RNA-based gene regulation and could one day help scientists better understand and even control gene expression in diseases.
Publication
Mapping effective microRNA pairing beyond the seed using abasic modifications.
Kosek DM, Petzold K, Andersson ER
Nucleic Acids Res 2025 Apr;53(8):
