Endogenous single-stranded non-coding RNAs of roughly 21 to 23 nucleotides that fine-tune post-transcriptional gene expression across the human proteome by base-pairing to the 3' untranslated regions of target messenger RNAs. First discovered in 1993 by Rosalind Lee, Rhonda Feinbaum, and Victor Ambros as the heterochronic lin-4 RNA in Caenorhabditis elegans, and recognized across animal phyla when the conserved let-7 family was identified; human microRNA genes covered on this site are listed in the Regulatory MicroRNAs registry.
Class
Endogenous small post-transcriptional regulatory non-coding RNA
Seed-region (nucleotides 2–8) base-pairing to 3' UTRs driving translational repression and deadenylation
Clinical / Biotech Use
Circulating liquid-biopsy cancer biomarkers, anti-miR oligonucleotide inhibitors (antagomirs), and miRNA mimics
Structure & Biogenesis
Transcribed in the nucleus by RNA polymerase II (either from dedicated intergenic genes or from the introns of host pre-mRNAs) as long capped and polyadenylated primary transcripts (pri-miRNAs) folding into imperfect stem-loop hairpins.
The nuclear Microprocessor complex — composed of the RNase III endonuclease Drosha and its double-stranded RNA-binding cofactor DGCR8 — crops the stem-loop base to release a ~65-to-70-nucleotide precursor hairpin (pre-miRNA) bearing a 2-nucleotide 3' overhang.
Exportin-5 transports the pre-miRNA into the cytoplasm in a Ran-GTP-dependent manner, where the cytoplasmic RNase III enzyme Dicer cleaves off the terminal loop to yield an ~22-bp miRNA/miRNA* duplex.
Mechanism of Action
One strand of the duplex (the mature guide miRNA, designated -5p or -3p by its hairpin arm of origin) is loaded into an Argonaute protein (AGO1, AGO2, AGO3, or AGO4) to form the miRNA-induced silencing complex (miRISC), while the passenger strand is discarded. Unlike small interfering RNAs (siRNAs), which require full-length complementarity to trigger endonucleolytic cleavage, animal miRNAs pair primarily through their 5' seed region (nucleotides 2–8). Seed pairing recruits the scaffold protein TNRC6 (GW182), which brings in the PAN2–PAN3 and CCR4–NOT deadenylase complexes to shorten the mRNA poly(A) tail, block translation initiation at the ribosome, and commit the transcript to decapping and 5'-to-3' exonucleolytic decay.
Biological & Regulatory Roles
Because a 7-nucleotide seed match can occur across hundreds of 3' UTRs, a single microRNA family acts as a network hub buffering developmental switches, cell-cycle checkpoints, and differentiation lineages.
Tumor-suppressor microRNAs such as let-7 (which represses RAS and MYC), miR-15a, and miR-16 (which target BCL2) restrain proliferation, whereas oncogenic microRNAs ("oncomiRs") such as miR-21 (targeting PTEN) and the miR-17~92 cluster promote survival and metastasis.
Interactions & Complexes
Sequestered and titrated in the cytosol by competing endogenous RNAs, including long non-coding RNAs and backspliced circular RNAs that display tandem seed-matching binding sites.
Therapeutic & Biotechnology Applications
Extracellular miRNAs packaged inside exosomes or bound to Argonaute complexes circulate stably in plasma, resisting serum ribonucleases and serving as non-invasive diagnostic biomarkers for tissue injury and malignancy.
Chemically modified antisense oligonucleotides (anti-miRs / antagomirs, such as miravirsen targeting liver-specific miR-122) and synthetic miRNA mimics target dysregulated miRNA axes in fibrosis, viral infection, and oncology.