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

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.