Regulation of miRNA strand selection: follow the leader?

Meijer, H. A., Smith, E. M. and Bushell, M. (2014) Regulation of miRNA strand selection: follow the leader? Biochemical Society Transactions, 42(4), pp. 1135-1140. (doi: 10.1042/BST20140142) (PMID:25110015)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Meijer, H. A., Smith, E. M., and Bushell, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Biochemical Society Transactions
• Publisher: Portland Press
• ISSN: 0300-5127
• ISSN (Online): 1470-8752