April 15, 2015

Publication: GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic AMP-GMP

Colleen A. Kellenberger, Stephen C. Wilson, Scott F. Hickey, Tania L. Gonzalez, Yichi Su, Zachary F. Hallberg, Thomas F. Brewer, Anthony T. Iavarone, Hans K. Carlson, Yu-Fang Hsieh, and Ming C. Hammond

PNAS April 28, 2015 112 (17) 5383-5388; published ahead of print April 6, 2015 https://doi.org/10.1073/pnas.1419328112

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Highlight

  • We discovered a riboswitch subclass that prefers to bind cyclic AMP-GMP (cAG). Previously, it was assumed to bind cyclic di-GMP (cdiG) due to sequence similarity.
  • The anaerobic bacterium Geobacter sulfurreducens contains an operon regulated by the cAG-binding riboswitch.
  • Geobacter sulfurreducensand also produces cAG.
  • We developed a method to detect cAG inside living cells, a useful biotechnological tool to study cAG signaling.

Abstract

Cyclic dinucleotides are an expanding class of signaling molecules that control many aspects of bacterial physiology. A synthase for cyclic AMP-GMP (cAG, also referenced as 3′-5′, 3′-5′ cGAMP) called DncV is associated with hyperinfectivity of Vibrio cholerae but has not been found in many bacteria, raising questions about the prevalence and function of cAG signaling. We have discovered that the environmental bacterium Geobacter sulfurreducens produces cAG and uses a subset of GEMM-I class riboswitches (GEMM-Ib, Genes for the Environment, Membranes, and Motility) as specific receptors for cAG. GEMM-Ib riboswitches regulate genes associated with extracellular electron transfer; thus cAG signaling may control aspects of bacterial electrophysiology. These findings expand the role of cAG beyond organisms that harbor DncV and beyond pathogenesis to microbial geochemistry, which is important to environmental remediation and microbial fuel cell development. Finally, we have developed an RNA-based fluorescent biosensor for live-cell imaging of cAG. This selective, genetically encodable biosensor will be useful to probe the biochemistry and cell biology of cAG signaling in diverse bacteria.

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