• Mature miRNAs are present in the nucleus and can regulate gene expression at the transcriptional level, expanding their canonical cytoplasmic roles.
• Nuclear miRNAs interact with DNA, RNA, and proteins, forming nuclear miRISCs that modulate gene transcription and ncRNA maturation.
• The presence of Ago proteins in the nucleus supports the formation of functional nuclear miRISCs, enhancing the efficiency of miRNA-mediated regulation.
• Understanding nuclear miRNA functions may reveal new therapeutic targets and biomarkers for diseases, given their involvement in various pathological processes.