Enzymatic Degradation of Linear Dinucleotide Intermediates of Cyclic Dinucleotides

Abstract

Bacterial cyclic dinucleotides (cyclic di-GMP, cyclic di-AMP, and cyclic GMP-AMP) are signaling molecules that bind to intracellular receptors to regulate a wide range of processes. In response to environmental changes, bacteria alter the rate of both synthesis and degradation to control the concentration of cyclic dinucleotides. Degradation occurs in a two-step process. The first step is carried out by enzymes specific to each cyclic dinucleotide and results in the formation of a linear dinucleotide. The second step is the hydrolysis of the linear dinucleotide into mononucleotides. Some phosphodiesterases that degrade the cyclic dinucleotide to the linear form are also capable of further hydrolysis to mononucleotides in vitro. However, not all species that utilize cyclic-dinucleotide signaling have these enzymes. Recently, it was shown that exoribonucleases specific for very short RNA substrates also degrade the linear dinucleotide intermediates of cyclic dinucleotide turnover. These results indicate that there is a potential overlap between RNA degradation and cyclic dinucleotide signaling suggesting the possibility of cross talk between signaling and RNA turnover.