ArticleNucleic acids research2015
Paradoxical suppression of small RNA activity at high Hfq concentrations due to random-order binding.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Article
- Gene knockdown by structure defined single-stem loop small non-coding RNAs with programmable regulatory activities.Synthetic and systems biotechnology · 2023Article
- A modular RNA interference system for multiplexed gene regulation.Nucleic acids research · 2022Article
- How global RNA-binding proteins coordinate the behaviour of RNA regulons: An information approach.Computational and structural biotechnology journal · 2022Article
- Stepwise sRNA targeting of structured bacterial mRNAs leads to abortive annealing.Molecular cell · 2021Article
- Synthetic negative feedback circuits using engineered small RNAs.Nucleic acids research · 2018Article
- Article
- Nucleoid and cytoplasmic localization of small RNAs in Escherichia coli.Nucleic acids research · 2017Article
- The Phosphorolytic Exoribonucleases Polynucleotide Phosphorylase and RNase PH Stabilize sRNAs and Facilitate Regulation of Their mRNA Targets.Journal of bacteriology · 2016Article
- The unmasking of 'junk' RNA reveals novel sRNAs: from processed RNA fragments to marooned riboswitches.Current opinion in microbiology · 2016Review
- Hfq: the flexible RNA matchmaker.Current opinion in microbiology · 2016Review
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Authors and funding
4 authors.
Funding
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Abstract
Small RNAs (sRNAs) are important regulators of gene expression during bacterial stress and pathogenesis. sRNAs act by forming duplexes with mRNAs to alter their translation and degradation. In some bacteria, duplex formation is mediated by the Hfq protein, which can bind the sRNA and mRNA in each pair in a random order. Here we investigate the consequences of this random-order binding and experimentally demonstrate that it can counterintuitively cause high Hfq concentrations to suppress rather than promote sRNA activity in Escherichia coli. As a result, maximum sRNA activity occurs when the Hfq concentration is neither too low nor too high relative to the sRNA and mRNA concentrations ('Hfq set-point'). We further show with models and experiments that random-order binding combined with the formation of a dead-end mRNA-Hfq complex causes high concentrations of an mRNA to inhibit its own duplex formation by sequestering Hfq. In such cases, maximum sRNA activity requires an optimal mRNA concentration ('mRNA set-point') as well as an optimal Hfq concentration. The Hfq and mRNA set-points generate novel regulatory properties that can be harnessed by native and synthetic gene circuits to provide greater control over sRNA activity, generate non-monotonic responses and enhance the robustness of expression.
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