4.8 Article

Dynamic features of gene expression control by small regulatory RNAs

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0901466106

Keywords

gene regulation; mRNA silencing; RyhB; small RNA; Spot42

Funding

  1. Canadian Institute for Health Research [MOP69005]
  2. Intramural Research Program of the National Institutes of Health
  3. National Cancer Institute
  4. Center for Cancer Research
  5. Danish National Research Foundation
  6. Hungarian Scientific Research Fund [PD75496]
  7. Canadian Institute for Health Research New Investigator Scholar
  8. Hungarian Academy of Sciences

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Small regulatory RNAs (sRNAs) in eukaryotes and bacteria play an important role in the regulation of gene expression either by binding to regulatory proteins or directly to target mRNAs. Two of the best-characterized bacterial sRNAs, Spot42 and RyhB, form a complementary pair with the ribosome binding region of their target mRNAs, thereby inhibiting translation or promoting mRNA degradation. To investigate the steady-state and dynamic potential of such sRNAs, we examine the 2 key parameters characterizing sRNA regulation: the capacity to overexpress the sRNA relative to its target mRNA and the speed at which the target mRNA is irreversibly inactivated. We demonstrate different methods to determine these 2 key parameters, for Spot42 and RyhB, which combine biochemical and genetic experiments with computational analysis. We have developed a mathematical model that describes the functional properties of sRNAs with various characteristic parameters. We observed that Spot42 and RyhB function in distinctive parameter regimes, which result in divergent mechanisms.

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