MicroRNA

MicroRNAs (miRNAs) are a naturally occurring class of small (approximately 22 nucleotides long) non-coding RNAs that regulate post-transcriptional gene expression to control cellular processes, development, cell differentiation, and homeostasis. MicroRNAs are essential for embryo, cell, and tissue development, regulating cell differentiation, proliferation, and apoptosis, hence their importance in human reproduction. Meanwhile, abnormal expression or function of miRNAs are found to be closely associated with the occurrence or development of various human diseases, including cancers. In light of their significant roles in physiology and pathology, miRNAs are emerging as novel biomolecular targets for chemical-biological studies, including regulation and detection.

Multiple steps are involved in the generation of miRNAs. Most miRNAs are produced by the canonical biogenesis pathway, which involves transcription by RNA polymerase II to make a primary transcript (pri-miRNA) and cleavage by the microprocessor complex to yield a hairpin precursor miRNA (pre-miRNA) in the nucleus. The pre-miRNA is then exported into the cytoplasm, where cleavage by the enzyme Dicer creates a double-stranded RNA duplex. Only a single strand from the double-stranded RNA duplex forms the mature miRNA and is incorporated into the RNA-induced silencing complex (RISC), which guides the binding of Argonaute (AGO) proteins in the RISC to the 3’untranslated region (UTR) to either repress protein translation or promote mRNA degradation. In addition to canonical miRNA biogenesis pathways, non-canonical microprocessor-independent or Dicer-independent miRNA biogenesis pathways also exist. Despite miRNAs being mostly involved in the down-regulation of gene expression, there are reports of miRNAs promoting gene expression. In addition, relationships between miRNAs and their targets are not always one-to-one in a specific cell type. In fact, a single miRNA may regulate many mRNA targets, and conversely, a single mRNA target also can be regulated by many miRNAs.