Organisms use 3′,5′-cyclic nucleotides monophosphates as intracellular signaling molecules, allowing them to integrate external stimuli and control numerous pathways. Reports have identified 2′,3′-cyclic nucleotide monophosphates (2′,3′-cNMPs) in eukaryotes and linked levels to cellular stress/wounding (E. Jackson, 2011; T. Van Damme, et al, 2014). We’ve recently discovered that 2′,3′-cNMPs are produced in bacteria and are products of a previously undiscovered RNA degradation pathways involving RNase I. Furthermore, we’ve found that 2′,3′-cNMP levels are linked to biofilm formation, suggesting that these nucleotides regulate important bacterial phenotypes.

 

We’re currently working to improve our understanding of the physiological roles of 2′,3′-cNMPs, as well as the enzymes involved in 2′,3′-cNMP metabolism and sensor proteins responsible for monitoring the intracellular concentration. To do so, we’ve developed molecular tools to regulate 2′,3′-cNMP levels in bacteria and are using these tools to probe the cellular effects and proteins involved. 

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Papers related to the 2′,3′-cNMP project:

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• Marotta, N.J.; Weinert, E.E. (2023) Insights into the metabolism, signaling, and physiological effects of 2’,3’-cyclic nucleotide monophosphates in bacteria. Crit. Rev. Biochem. Mol. Biol. DOI: 10.1080/10409238.2023.2290473

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• Chauhan, S.S.; Weinert, E.E. (2023) Generation of nucleotide-linked resins for identification of novel binding proteins. Methods Enzymol. 679, 323-330. DOI: 10.1016/bs.mie.2022.08.052

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• Chauhan, S.S.; Marotta, N.K.; Karls, A.C.; Weinert, E.E. (2022) Binding of 2',3'-Cyclic Nucleotide Monophosphates to Bacterial Ribosomes Inhibits Translation. ACS Cent. Sci. DOI: 10.1021/acscentsci.2c00681

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• Duggal, Y.;^ Kurasz, J.E.^; Fontaine, B.M.^; Marotta, N.J.; Chauhan, S.S.; Karls, A.C.; Weinert, E.E. (2022) Cellular Effects of 2’,3’-Cyclic Nucleotide Monophosphates in Gram-Negative Bacteria. J. Bacteriol. 204, e00208-21. DOI: 10.1128/JB.00208-21​​

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• Duggal, Y.^; Fontaine, B.M.^; Dailey, D.M.*; Ning, G.; Weinert, E.E. (2020) RNase I Modulates Escherichia coli Motility, Metabolism, and Resistance. ACS Chem. Biol. 15, 1996-2004. DOI: 10.1021/acschembio.0c00390

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• Fontaine, B.M.; Duggal, Y.; Weinert, E.E. (2020) 2',3'-Cyclic Mononucleotide Metabolism and Possible Role in Bacterial Physiology. In Microbial Cyclic Di-Nucleotide Signaling. Chou, S.-H.; Guiliani, N.; Lee, V.T.; Romling, U.; Eds. Ch. 36, 627-637.

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• Fontaine, B.M.; Martin, K.S.; Garcia-Rodriguez, J.M.; Jung, C.; Briggs, L.; Southwell, J.E.; Jia, X.; Weinert, E.E. (2018) RNase I Regulates E. coli 2′,3′-Cyclic Nucleotide Monophosphate Levels and Biofilm Formation. Biochem. J. 475, 1491-1506. DOI: 10.1042/BCJ20170906

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• Jia, X.; Fontaine, B.M.; Strobel, F.; Weinert, E.E. (2014) A Facile and Sensitive Method for Quantification of Cyclic Nucleotide Monophosphates in Mammalian Organs: Basal Levels of Eight cNMPs and Identification of cIMP. Biomolecules, 4, 1070-1092. DOI: 10.3390/biom4041070