Sensing the needs: Molecular basis of miRNA regulatory role of ELAVL protein HuR.

Regulation of miRNAs in mammalian cells-including their expression, activity, transport, storage, and export-is vital for the control of gene expression and cellular function. This process is affected by external stimuli, such as stress or pathogen exposure, and regulated by interactions among miRNAs, target mRNAs, and RNA-binding proteins. Human ELAVL1 HuR, a stress-responsive nuclear protein that can shuttle to the cytoplasm, modulates miRNA activity, storage, and export in a contextual manner. As an AU-rich element (ARE)-containing RNA-binding protein, HuR plays multimodal roles in miRNA regulation. How HuR manages these diverse functions under stress, infection, or in cancer remains a key area of research. This review explores the miRNA-regulatory role of HuR across subcellular compartments, focusing on how its localization affects miRNA export or storage, and discusses potential mechanisms underlying HuR's versatile functions, including mRNA stabilization and miRNA homeostasis. This review discusses how post-translational modifications of HuR or its partners affect miRNA activity, suggesting that HuR serves as a miRNA sensor and linking HuR-related miRNA regulation to human diseases, thereby positioning HuR as a druggable target for controlling miRNA activity and target gene expression.