title: Regulation of miRNA strand selection: follow the leader?
abstract: miRNA strand selection is the process that determines which of the two strands in a miRNA duplex becomes the active strand that is incorporated into the RISC (RNA-induced silencing complex) (named the guide strand, leading strand or miR) and which one gets degraded (the passenger strand or miR*). Thermodynamic features of the duplex appear to play an important role in this decision; the strand with the weakest binding at its 5'-end is more likely to become the guide strand. Other key characteristics of human miRNA guide strands are a U-bias at the 5'-end and an excess of purines, whereas the passenger strands have a C-bias at the 5'-end and an excess of pyrimidines. Several proteins are known to play a role in strand selection [Ago (Argonaute), DICER, TRBP (trans-activation response RNA-binding protein), PACT (protein activator of dsRNA-dependent protein kinase) and Xrn-1/2]; however, the mechanisms by which these proteins act are largely unknown. For several miRNAs the miR/miR* ratio varies dependent on cell type, developmental stage and in different disease states, suggesting that strand selection is a tightly controlled process. The present review discusses our current knowledge regarding the factors and processes involved in strand selection and the many questions that still remain.
authors.affiliation: *Medical Research Council (MRC) Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, U.K.
authors.forename: Hedda A
authors.initials: HA
authors.lastname: Meijer
authors.affiliation: *Medical Research Council (MRC) Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, U.K.
authors.forename: Ewan M
authors.initials: EM
authors.lastname: Smith
authors.affiliation: *Medical Research Council (MRC) Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, U.K.
authors.forename: Martin
authors.initials: M
authors.lastname: Bushell
mesh_terms: D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D011687:Purines / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D035683:MicroRNAs; D011687:Purines