c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

Taylor Van Gundy; Dhara Patel; Bruce E. Bowler; Michael T. Rothfuss; Allie J. Hall; Christopher Davies; Laura S. Hall; Dan Drecktrah; Richard T. Marconi; D. Scott Samuels; Meghan C. Lybecker

doi:10.1111/mmi.15066

c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

Taylor Van Gundy
, Dhara Patel
, Bruce E. Bowler
, Michael T. Rothfuss
, Allie J. Hall
, Christopher Davies
, Laura S. Hall
, Dan Drecktrah
, Richard T. Marconi
, D. Scott Samuels
, Meghan C. Lybecker

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 survival in the tick; 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.

Original language	English
Pages (from-to)	711-727
Number of pages	17
Journal	Molecular Microbiology
Volume	119
Issue number	6
DOIs	https://doi.org/10.1111/mmi.15066
State	Published - Jun 2023

Funding

This work was supported by National Institutes of Health grant R01 AI130247 to DSS, MCL, and DD. We thank Bob Gilmore, Kevin Brandt, and Brittany Armstrong for thoughtful and critical reading of the manuscript. We thank Jeremy Bono, Jean-Marc Lanchy, James Kovaks, and Crystal Vander Zanden for useful discussions. We thank Robert Landick for the RL211 strain. We thank Irina Goodrich for excellent technical support. The findings and conclusions in this report are those of the authors and do not represent the official position of the Centers for Disease Control and Prevention.

Funders	Funder number
R01 AI130247
Centers for Disease Control and Prevention

Keywords

Borrelia burgdorferi
Lyme disease
PlzA
RNA chaperone
c-di-GMP
Bacterial Proteins/metabolism
Ixodes
RNA/metabolism
Borrelia burgdorferi/metabolism
Lyme Disease/genetics
Borrelia burgdorferi Group/genetics

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10.1111/mmi.15066

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title = "c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete",

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 survival in the tick; 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.",

keywords = "Borrelia burgdorferi, Lyme disease, PlzA, RNA chaperone, c-di-GMP, Bacterial Proteins/metabolism, Ixodes, RNA/metabolism, Borrelia burgdorferi/metabolism, Lyme Disease/genetics, Borrelia burgdorferi Group/genetics",

author = "Taylor Van Gundy and Dhara Patel and Bowler, \{Bruce E.\} and Rothfuss, \{Michael T.\} and Hall, \{Allie J.\} and Christopher Davies and Hall, \{Laura S.\} and Dan Drecktrah and Marconi, \{Richard T.\} and Samuels, \{D. Scott\} and Lybecker, \{Meghan C.\}",

note = "{\textcopyright} 2023 The Authors. Molecular Microbiology published by John Wiley \& Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.",

year = "2023",

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doi = "10.1111/mmi.15066",

language = "English",

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pages = "711--727",

journal = "Molecular Microbiology",

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T1 - c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

AU - Van Gundy, Taylor

AU - Patel, Dhara

AU - Bowler, Bruce E.

AU - Rothfuss, Michael T.

AU - Hall, Allie J.

AU - Davies, Christopher

AU - Hall, Laura S.

AU - Drecktrah, Dan

AU - Marconi, Richard T.

AU - Samuels, D. Scott

AU - Lybecker, Meghan C.

PY - 2023/6

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N2 - 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 survival in the tick; 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.

AB - 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 survival in the tick; 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.

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KW - RNA chaperone

KW - c-di-GMP

KW - Bacterial Proteins/metabolism

KW - Ixodes

KW - RNA/metabolism

KW - Borrelia burgdorferi/metabolism

KW - Lyme Disease/genetics

KW - Borrelia burgdorferi Group/genetics

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AN - SCOPUS:85153538335

SN - 0950-382X

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SP - 711

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JO - Molecular Microbiology

JF - Molecular Microbiology

IS - 6

ER -

c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

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