Researchers from Karolinska Institutet and Uppsala University have developed a novel technique to investigate how microRNAs (miRNAs), small RNA molecules that regulate gene expression, control the activation or repression of genes. Traditionally, the ‘seed’ region of miRNAs was considered the main functional part responsible for binding messenger RNAs and inhibiting protein production. However, this new study focused on the less understood ‘tail end’ of the miRNA molecule, specifically miR-34a, by altering two tiny nucleotide positions to prevent binding to target RNA regions. The results showed that while most genes were unaffected, a distinct subset of gene targets exhibited significantly reduced regulation, demonstrating that regions beyond the seed are crucial for fine-tuning gene activity. Additionally, the research revealed that certain structural mismatches in miRNA binding are more disruptive than others, providing valuable insights for designing improved miRNA-based diagnostics and therapies. Published in Nucleic Acids Research, this work advances the understanding of RNA-based gene regulation and offers potential pathways for better control of gene expression in diseases such as cancer and neurodevelopmental disorders.
Original title: Tiny tweaks to microRNAs uncover big insights into gene control
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