Journal
BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 42, Issue -, Pages 1135-1140Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BST20140142
Keywords
guide strand; isomiR; leading strand; miR; miRNA biogenesis; passenger strand
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Funding
- Biotechnology and Biological Sciences Research Council [BB/F011806/1] Funding Source: researchfish
- Medical Research Council [MC_EX_G0902052, MC_UP_A600_1024] Funding Source: researchfish
- BBSRC [BB/F011806/1] Funding Source: UKRI
- MRC [MC_UP_A600_1024, MC_EX_G0902052] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F011806/1] Funding Source: Medline
- Medical Research Council [MC_EX_G0902052, MC_UP_A600_1024] Funding Source: Medline
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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.
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