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c-di-GMP regulates RNA chaperone activity of PlzA in the Lyme disease spirochete
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  • Meghan C. Lybecker,
  • Taylor Van Gundy,
  • Dhara Patel,
  • Bruce E. Bowler,
  • Michael T. Rothfuss,
  • Allie J. Hall,
  • Christopher Davies,
  • Laura Hall,
  • Dan Drecktrah,
  • Richard T. Marconi,
  • D Scott Samuels
Meghan C. Lybecker
National Center for Emerging and Zoonotic Infectious Diseases Division of Vector Borne Diseases

Corresponding Author:[email protected]

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Taylor Van Gundy
National Center for Emerging and Zoonotic Infectious Diseases Division of Vector Borne Diseases
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Dhara Patel
Virginia Commonwealth University Department of Microbiology and Immunology
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Bruce E. Bowler
University of Montana
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Michael T. Rothfuss
University of Montana
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Allie J. Hall
National Center for Emerging and Zoonotic Infectious Diseases Division of Vector Borne Diseases
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Christopher Davies
University of Southern Alabama
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Laura Hall
University of Montana Division of Biological Sciences
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Dan Drecktrah
University of Montana Division of Biological Sciences
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Richard T. Marconi
Virginia Commonwealth University Department of Microbiology and Immunology
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D Scott Samuels
University of Montana
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Abstract

PlzA is a c-di-GMP-binding protein crucial for adaptation of the Lyme disease spirochete Borrelia ( Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo-PlzA is important for vertebrate infection, while liganded holo-PlzA is important for tick acquisition; however, the biological function of PlzA has remained enigmatic. Here we report that PlzA has RNA chaperone activity that is inhibited by c-di-GMP binding. Holo- and apo-PlzA bind RNA and accelerate RNA annealing, while only apo-PlzA can strand displace and unwind double-stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N- and C-terminal domains that are required for RNA binding and unwinding activity. Our findings illuminate c-di-GMP as a switch controlling the RNA chaperone activity of PlzA and we propose that complex RNA-mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle.
04 Apr 2023Submitted to Molecular Microbiology
04 Apr 2023Submission Checks Completed
04 Apr 2023Assigned to Editor
05 Apr 2023Editorial Decision: Revise Minor
10 Apr 20231st Revision Received
10 Apr 2023Submission Checks Completed
10 Apr 2023Assigned to Editor
10 Apr 2023Editorial Decision: Accept