Regulation of miRNA strand selection: follow the leader?. (11th August 2014)

• Record Type: Journal Article
• Authors: Meijer, Hedda A.; Smith, Ewan M.; Bushell, Martin
• Is Part Of: Biochemical Society transactions. Volume 42:Number 4(2014)
• Page Start: 1135
• Page End: 1140
• Publication Date: 2014-08-11
• Subjects: guide strand -- isomiR -- leading strand -- miR* -- miRNA biogenesis -- passenger strand; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20140142
• Languages: English
• ISSNs: 0300-5127

Abstract

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.