A subset of exoribonucleases serve as degradative enzymes for pGpG in c-di-GMP signaling

Mona W. Orr, Cordelia A. Weiss, Geoffrey B. Severin, Husan Turdiev, Soo Kyoung Kim, Asan Turdiev, Kuanqing Liu, Benjamin P Tu, Christopher M. Waters, Wade C. Winkler, Vincent T. Lee

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that regulates processes, such as biofilm formation and virulence. During degradation, c-di-GMP is first linearized to 5′-phosphoguanylyl-(3′,5′)-guanosine (pGpG) and subsequently hydrolyzed to two GMPs by a previously unknown enzyme, which was recently identified in Pseudomonas aeruginosa as the 3′-to-5′ exoribonuclease oligoribonuclease (Orn). Mutants of orn accumulated pGpG, which inhibited the linearization of c-di-GMP. This product inhibition led to elevated c-di-GMP levels, resulting in increased aggregate and biofilm formation. Thus, the hydrolysis of pGpG is crucial to the maintenance of c-di-GMP homeostasis. How species that utilize c-di- GMP signaling but lack an orn ortholog hydrolyze pGpG remains unknown. Because Orn is an exoribonuclease, we asked whether pGpG hydrolysis can be carried out by genes that encode protein domains found in exoribonucleases. From a screen of these genes from Vibrio cholerae and Bacillus anthracis, we found that only enzymes known to cleave oligoribonucleotides (orn and nrnA) rescued the P. aeruginosa δorn mutant phenotypes to the wild type. Thus, we tested additional RNases with demonstrated activity against short oligoribonucleotides. These experiments show that only exoribonucleases previously reported to degrade short RNAs (nrnA, nrnB, nrnC, and orn) can also hydrolyze pGpG. A B. subtilis nrnA nrnB mutant had elevated c-di- GMP, suggesting that these two genes serve as the primary enzymes to degrade pGpG. These results indicate that the requirement for pGpG hydrolysis to complete c-di-GMP signaling is conserved across species. The final steps of RNA turnover and c-di-GMP turnover appear to converge at a subset of RNases specific for short oligoribonucleotides.

Original languageEnglish (US)
Article numbere00300
JournalJournal of bacteriology
Issue number24
StatePublished - Dec 1 2018


  • Cyclic-di-GMP signaling
  • Dinucleotide hydrolysis
  • NanoRNase
  • PApA
  • PGpG
  • RNA degradation

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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