Rare Variants of the FMN Riboswitch Class in and Other Bacteria Exhibit Altered Ligand Specificity

Overview

Journal RNA

Specialty Molecular Biology

Date 2018 Oct 6

PMID 30287481

Citations 14

Authors

Ruben M Atilho

Kevin R Perkins

Ronald R Breaker

Affiliations

Soon will be listed here.

Abstract

Many bacteria use flavin mononucleotide (FMN) riboswitches to control the expression of genes responsible for the biosynthesis and transport of this enzyme cofactor or its precursor, riboflavin. Rare variants of FMN riboswitches found in strains of and some other bacteria typically control the expression of proteins annotated as transporters, including multidrug efflux pumps. These RNAs no longer recognize FMN, and differ from the original riboswitch consensus sequence at nucleotide positions normally involved in binding of the ribityl and phosphate moieties of the cofactor. Representatives of one of the two variant subtypes were found to bind the FMN precursor riboflavin and the FMN degradation products lumiflavin and lumichrome. Although the biologically relevant ligand sensed by these variant FMN riboswitches remains uncertain, our findings suggest that many strains of might use rare riboswitches to sense flavin degradation products and activate transporters for their detoxification.

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References

Lewis K . Translocases: a bacterial tunnel for drugs and proteins. Curr Biol. 2000; 10(18):R678-81. DOI: 10.1016/s0960-9822(00)00682-5. View

Weinberg Z, Breaker R . R2R--software to speed the depiction of aesthetic consensus RNA secondary structures. BMC Bioinformatics. 2011; 12:3. PMC: 3023696. DOI: 10.1186/1471-2105-12-3. View

Gutierrez-Preciado A, Torres A, Merino E, Bonomi H, Goldbaum F, Garcia-Angulo V . Extensive Identification of Bacterial Riboflavin Transporters and Their Distribution across Bacterial Species. PLoS One. 2015; 10(5):e0126124. PMC: 4418817. DOI: 10.1371/journal.pone.0126124. View

Grininger M, Zeth K, Oesterhelt D . Dodecins: a family of lumichrome binding proteins. J Mol Biol. 2006; 357(3):842-57. DOI: 10.1016/j.jmb.2005.12.072. View

Nawrocki E, Burge S, Bateman A, Daub J, Eberhardt R, Eddy S . Rfam 12.0: updates to the RNA families database. Nucleic Acids Res. 2014; 43(Database issue):D130-7. PMC: 4383904. DOI: 10.1093/nar/gku1063. View

Howe J, Wang H, Fischmann T, Balibar C, Xiao L, Galgoci A . Selective small-molecule inhibition of an RNA structural element. Nature. 2015; 526(7575):672-7. DOI: 10.1038/nature15542. View

Robinson A, Thomas N, Morrison E, Balthazor B, Henzler-Wildman K . New free-exchange model of EmrE transport. Proc Natl Acad Sci U S A. 2017; 114(47):E10083-E10091. PMC: 5703289. DOI: 10.1073/pnas.1708671114. View

Grininger M, Staudt H, Johansson P, Wachtveitl J, Oesterhelt D . Dodecin is the key player in flavin homeostasis of archaea. J Biol Chem. 2009; 284(19):13068-76. PMC: 2676039. DOI: 10.1074/jbc.M808063200. View

Weinberg Z, Lunse C, Corbino K, Ames T, Nelson J, Roth A . Detection of 224 candidate structured RNAs by comparative analysis of specific subsets of intergenic regions. Nucleic Acids Res. 2017; 45(18):10811-10823. PMC: 5737381. DOI: 10.1093/nar/gkx699. View

10.

Stockbridge R, Robertson J, Kolmakova-Partensky L, Miller C . A family of fluoride-specific ion channels with dual-topology architecture. Elife. 2013; 2:e01084. PMC: 3755343. DOI: 10.7554/eLife.01084. View

11.

Sherlock M, Sudarsan N, Breaker R . Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems. Proc Natl Acad Sci U S A. 2018; 115(23):6052-6057. PMC: 6003355. DOI: 10.1073/pnas.1720406115. View

12.

Ren A, Rajashankar K, Patel D . Fluoride ion encapsulation by Mg2+ ions and phosphates in a fluoride riboswitch. Nature. 2012; 486(7401):85-9. PMC: 3744881. DOI: 10.1038/nature11152. View

13.

Garcia Angulo V, Bonomi H, Posadas D, Serer M, Torres A, Zorreguieta A . Identification and characterization of RibN, a novel family of riboflavin transporters from Rhizobium leguminosarum and other proteobacteria. J Bacteriol. 2013; 195(20):4611-9. PMC: 3807449. DOI: 10.1128/JB.00644-13. View

14.

Soukup G, Breaker R . Relationship between internucleotide linkage geometry and the stability of RNA. RNA. 1999; 5(10):1308-25. PMC: 1369853. DOI: 10.1017/s1355838299990891. View

15.

Linster C, Van Schaftingen E, Hanson A . Metabolite damage and its repair or pre-emption. Nat Chem Biol. 2013; 9(2):72-80. DOI: 10.1038/nchembio.1141. View

16.

Nelson J, Sudarsan N, Phillips G, Stav S, Lunse C, McCown P . Control of bacterial exoelectrogenesis by c-AMP-GMP. Proc Natl Acad Sci U S A. 2015; 112(17):5389-94. PMC: 4418907. DOI: 10.1073/pnas.1419264112. View

17.

Baker J, Sudarsan N, Weinberg Z, Roth A, Stockbridge R, Breaker R . Widespread genetic switches and toxicity resistance proteins for fluoride. Science. 2011; 335(6065):233-235. PMC: 4140402. DOI: 10.1126/science.1215063. View

18.

Kellenberger C, Wilson S, Hickey S, Gonzalez T, Su Y, Hallberg Z . GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic AMP-GMP. Proc Natl Acad Sci U S A. 2015; 112(17):5383-8. PMC: 4418906. DOI: 10.1073/pnas.1419328112. View

19.

Mironov A, Gusarov I, Rafikov R, Lopez L, Shatalin K, Kreneva R . Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria. Cell. 2002; 111(5):747-56. DOI: 10.1016/s0092-8674(02)01134-0. View

20.

Grkovic S, Brown M, Roberts N, Paulsen I, Skurray R . QacR is a repressor protein that regulates expression of the Staphylococcus aureus multidrug efflux pump QacA. J Biol Chem. 1998; 273(29):18665-73. DOI: 10.1074/jbc.273.29.18665. View