microRNA

MicroRNA (miRNA) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. They are typically 21 to 24 nucleotides long and function by guiding a protein complex to complementary messenger RNA targets, often resulting in translational repression or mRNA degradation. miRNAs play roles in numerous biological processes, including development, differentiation, metabolism, and immune responses.

Most miRNA genes are transcribed by RNA polymerase II as primary transcripts containing hairpin structures. The nuclear microprocessor, comprising Drosha and DGCR8, cleaves these transcripts to yield precursor miRNAs (~70 nucleotides). Pre-miRNAs are exported to the cytoplasm by Exportin-5 and are further processed by Dicer to produce a miRNA duplex. One strand, the guide strand, is incorporated into the RNA-induced silencing complex (RISC) with Argonaute proteins, while the passenger strand is typically degraded. Target recognition relies largely on the seed region, nucleotides 2 through 8 of the miRNA, which pairs with complementary sequences in target mRNAs, commonly in the 3' untranslated region. Binding can block translation or promote mRNA decay, and a single miRNA can regulate many targets, while a single mRNA can be regulated by multiple miRNAs.

Biological significance and clinical relevance: miRNAs participate in development and tissue homeostasis and contribute to responses to stress and disease. Dysregulation of miRNA expression is associated with various conditions, including cancer, cardiovascular and neurological disorders. Because they are detectable in body fluids, miRNAs have potential as diagnostic biomarkers, and therapeutic approaches using miRNA mimics or inhibitors are under investigation.