Paradigm shift: microRNAs interact with target gene promoters to cause transcriptional gene activation or silencing.

MicroRNAs (miRNAs/miRs) are small (18-25 nucleotides in length), endogenous, non-coding RNAs that typically repress gene expression by interacting with the 3'untranslated regions (3'UTRs) of target mRNAs in the cytoplasm. While most of the scientific community still views miRNAs as repressors of gene expression, this review highlights their non-canonical novel role in the nucleus as activators or silencers of target gene transcription through miRNA-promoter interaction. The mechanistic details of the transcriptional role of miRNAs are yet to be elucidated, however, they can be explained by prospective models. In this review, we aim to discuss the different examples of transcriptional regulation by miRNAs and their possible mechanism of action, thereby offering a comprehensive perspective on the role of miRNAs in gene regulation and their importance in health and diseases.