miRNA regulation in brain tissue space: the 3′UTR perspective

MicroRNAs (miRNAs) are key regulators of gene expression in both health and disease. Their expression and regulatory functions are highly complex and spatiotemporally organized within tissues. In recent years, spatial transcriptomics has made significant progress in quantifying RNA expression at subcellular resolution in tissue sections. However, no current method can quantify miRNAs and their target 3' untranslated regions (3'UTRs) in space simultaneously. Furthermore, although 3'UTRs harbor critical miRNA target sites, 3'UTR isoform variation in space is largely unexplored. In this review, we discuss the role of miRNA-mediated regulation. We focus on neurodevelopment and neuronal function, where miRNAs and 3'UTRs have particularly complex and important functions. We summarize current experimental and computational approaches for spatial quantification of miRNAs and 3'UTRs, highlight existing challenges, and propose strategies for future research.