ArticleNucleic acids research2017
Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Mammalian therapeutic riboswitches: Engineering and custom ligands.Molecular therapy. Nucleic acids · 2026Review
- An RNA Motif That Enables Optozyme Control and Light-Dependent Gene Expression in Bacteria and Mammalian Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Sensing intracellular signatures with synthetic mRNAs.RNA biology · 2023Review
- Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Inducible nuclear import by TetR aptamer-controlled 3' splice site selection.RNA (New York, N.Y.) · 2021Article
- Translational control of enzyme scavenger expression with toxin-induced micro RNA switches.Scientific reports · 2021Article
- Optoribogenetic control of regulatory RNA molecules.Nature communications · 2020Article
- The complex formed between a synthetic RNA aptamer and the transcription repressor TetR is a structural and functional twin of the operator DNA-TetR regulator complex.Nucleic acids research · 2020Article
- Robust gene expression control in human cells with a novel universal TetR aptamer splicing module.Nucleic acids research · 2019Article
- Aptamer-based and aptazyme-based riboswitches in mammalian cells.Current opinion in chemical biology · 2019Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic RNA-based systems have increasingly been used for the regulation of eukaryotic gene expression. Due to their structural properties, riboregulators provide a convenient basis for the development of ligand-dependent controllable systems. Here, we demonstrate reversible conditional control of miRNA biogenesis with an aptamer domain as a sensing unit connected to a natural miRNA precursor for the first time. For the design of the pre-miR switch, we replaced the natural terminal loop with the TetR aptamer. Thus, the TetR aptamer was positioned close to the Dicer cleavage sites, which allowed sterical control over pre-miR processing by Dicer. Our design proved to be highly versatile, allowing us to regulate the biogenesis of three structurally different miRNAs: miR-126, -34a and -199a. Dicer cleavage was inhibited up to 143-fold via co-expression of the TetR protein, yet could be completely restored upon addition of doxycycline. Moreover, we showed the functionality of the pre-miR switches for gene regulation through the interaction of the respective miRNA with its specific target sequence. Our designed device is capable of robust and reversible control of miRNA abundance. Thus, we offer a novel investigational tool for functional miRNA analysis.
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