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.