The Biology of Free Guanidine As Revealed by Riboswitches

Breaker, Ronald R.; Atilho, Ruben M; Malkowski, Sarah N.; Nelson, Jelani; Sherlock, Madeline E.

doi:10.1021/acs.biochem.6b01269

Cited by 33 publications

(40 citation statements)

References 6 publications

(19 reference statements)

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“…Different riboswitch classes that sense the same ligand form unique architectures, carry distinct patterns of nucleotide sequence conservation, and exhibit unique phylogenetic distributions [6][7][8][9]. The ligand sensed by the highest number of riboswitch classes is the cofactor S-adenosylmethionine (SAM) ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches

et al. 2018

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Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species. SAM-VI aptamers selectively bind the cofactor SAM and strongly discriminate against SAH. The consensus sequence and structural model for SAM-VI share some features with the consensus model for the SAM-III riboswitch class, whose members are mainly found in lactic acid bacteria. However, there are sufficient differences between the two classes such that current bioinformatics methods separately cluster representatives of the two motifs. These findings highlight the abundance of RNA structures that can form to selectively recognize SAM, and showcase the ability of RNA to utilize diverse strategies to perform similar biological functions.

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Section: Introductionmentioning

confidence: 99%

SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches

et al. 2018

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“…A solid lead on the native role of the SMRs was provided by the recent discovery of bacterial operons dedicated to guanidinium (Gdm + ) metabolism (12)(13)(14)(15). These operons are controlled by Gdm + -binding riboswitches, which frequently up-regulate either enzymes that chemically modify Gdm + or membrane proteins from the SMR family (15). These riboswitches are widespread in both Gram-negative and Gram-positive bacteria, including firmicutes, cyanobacteria, actinobacteria, proteobacteria, and others.…”

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confidence: 99%

Guanidinium export is the primal function of SMR family transporters

Kermani

Macdonald

Gundepudi

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

117

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The small multidrug resistance (SMR) family of membrane proteins is prominent because of its rare dual topology architecture, simplicity, and small size. Its best studied member, EmrE, is an important model system in several fields related to membrane protein biology, from evolution to mechanism. But despite decades of work on these multidrug transporters, the native function of the SMR family has remained a mystery, and many highly similar SMR homologs do not transport drugs at all. Here we establish that representative SMR proteins, selected from each of the major clades in the phylogeny, function as guanidinium ion exporters. Drug-exporting SMRs are all clustered in a single minority clade. Using membrane transport experiments, we show that these guanidinium exporters, which we term Gdx, are very selective for guanidinium and strictly and stoichiometrically couple its export with the import of two protons. These findings draw important mechanistic distinctions with the notably promiscuous and weakly coupled drug exporters like EmrE.

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“…Secondly, riboswitches have been highlighted as a potential tool for bioremediation (Breaker et al . ). Nelson et al .…”

Section: Riboswitchesmentioning

confidence: 97%

“…A large amount of guanidine, which denatures protein structures by interacting with the peptide backbone to promote unfolded conformations (Jha and Marqusee ), has been released into the natural environment from the industrial production of, for example, plastics, explosives and automobile airbags (Breaker et al . ). Bioremediation could be carried out by a microbe engineered to express urea carboxylases (Kanamori et al .…”

Section: Riboswitchesmentioning

confidence: 97%

Applications and limitations of regulatoryRNAelements in synthetic biology and biotechnology

et al. 2019

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Summary Synthetic biology requires the design and implementation of novel enzymes, genetic circuits or even entire cells, which can be controlled by the user. RNA‐based regulatory elements have many important functional properties in this regard, such as their modular nature and their ability to respond to specific external stimuli. These properties have led to the widespread exploration of their use as gene regulation devices in synthetic biology. In this review, we focus on two major types of RNA elements: riboswitches and RNA thermometers (RNATs). We describe their general structure and function, before discussing their potential uses in synthetic biology (e.g. in the production of biofuels and biodegradable plastics). We also discuss their limitations, and novel strategies to implement RNA‐based regulatory devices in biotechnological applications. We close with a description of some common model organisms used in synthetic biology, with a focus on the current applications and limitations of RNA‐based regulation.

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The Biology of Free Guanidine As Revealed by Riboswitches

Cited by 33 publications

References 6 publications

SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches

SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches

Guanidinium export is the primal function of SMR family transporters

Applications and limitations of regulatoryRNAelements in synthetic biology and biotechnology

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