title: The microRNA Machinery.
abstract: MicroRNAs (miRNAs) are short (~22 nucleotides) single-stranded RNA molecules that primarily function to negatively regulate gene expression at the post-transcriptional level. miRNAs have thus been implicated in the regulation of a wide variety of normal cell functions and pathophysiological conditions. The miRNA machinery consists of a series of protein complexes which act to: (1) cleave the precursor-miRNA hairpin from its primary transcript (i.e. DROSHA and DGCR8); (2) traffic the miRNA hairpin between nucleus and cytoplasm (i.e. XPO5); (3) remove the loop sequence of the hairpin by a second nucleolytic cleavage reaction (i.e. DICER1); (4) facilitate loading of the mature miRNA sequence into an Argonaute protein (typically AGO2) as part of the RNA-Induced Silencing Complex (RISC); (5) guide the loaded RISC complex to complementary, or semi-complementary, target transcripts and (6) facilitate gene silencing via one of several possible mechanisms.
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. troberts@sbpdiscovery.org.|Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. troberts@sbpdiscovery.org.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Roberts
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000737:chemistry / Q000378:metabolism*; D002268:Carboxypeptidases / Q000737:chemistry / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D059367:RNA Cleavage; D034443:RNA Transport; D043244:Ribonuclease III / Q000737:chemistry / Q000378:metabolism*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D028884:Karyopherins; D035683:MicroRNAs; C446511:XPO5 protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D002268:Carboxypeptidases; C436327:SCPEP1 protein, human; D053487:DEAD-box RNA Helicases
keywords: AGO2; Argonaute; DGCR8; DICER1; Dicer; Drosha; Exportin-5; XPO5; microRNA