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.
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For any given miRNA, the proportion of AGO-loaded 5p or 3p strand varies greatly depending on the cell type or cellular environment, ranging from near equal proportions to predominantly one or the other.
“For any given miRNA, the proportion of AGO-loaded 5p or 3p strand varies greatly depending on the cell type or cellular environment, ranging from near equal proportions to predominantly one or the other (33).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [33]
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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation
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- Authors
- Meijer, H. A., Smith, E. M., & Bushell, M.
- Affiliations
- Medical Research Council (GB)
- ORCID
- Meijer, Hedda A.
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2014-08-01
- Volume
- 42
- Issue
- 4
- Pages
- 1135-1140
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W2009684321
- Cited by
- 233
- References
- 55
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 10 · 2023: 18 · 2022: 33 · 2021: 28 · 2020: 20 · 2019: 26 · 2018: 18 · 2017: 24 · 2016: 15 · 2015: 12
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Medical Research Council (MC_EX_G0902052)
- Biotechnology and Biological Sciences Research Council (BB/F011806/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- guide strand, passenger strand, RNA-induced silencing complex, Argonaute proteins, Dicer, TRBP, PACT, RNA interference, post-transcriptional regulation
- MeSH terms
- Humans, Models, Biological, Purines, Thermodynamics, MicroRNAs
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