An mRNA structure that controls gene expression by binding S-adenosylmethionine

Riboswitches are metabolite-binding RNA structures that serve as genetic control elements for certain messenger RNAs. These RNA switches have been identified in all three kingdoms of life and are typically responsible for the control of genes whose protein products are involved in the biosynthesis, transport or utilization of the target metabolite. Herein, we report that a highly conserved RNA domain found in bacteria serves as a riboswitch that responds to the coenzyme S-adenosylmethionine (SAM) with remarkably high affinity and specificity. SAM riboswitches undergo structural reorganization upon introduction of SAM, and these allosteric changes regulate the expression of 26 genes in Bacillus subtilis. This and related findings indicate that direct interaction between small metabolites and allosteric mRNAs is an important and widespread form of genetic regulation in bacteria.

[1]  Jeffrey E. Barrick,et al.  Riboswitches Control Fundamental Biochemical Pathways in Bacillus subtilis and Other Bacteria , 2003, Cell.

[2]  Vitaly Epshtein,et al.  The riboswitch-mediated control of sulfur metabolism in bacteria , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Gary D. Stormo,et al.  Do mRNAs act as direct sensors of small molecules to control their expression? , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Gelfand,et al.  Comparative Genomics of Thiamin Biosynthesis in Procaryotes , 2002, The Journal of Biological Chemistry.

[5]  L. Samson,et al.  Influence of S-Adenosylmethionine Pool Size on Spontaneous Mutation, Dam Methylation, and Cell Growth ofEscherichia coli , 1999, Journal of bacteriology.

[6]  A. Fersht.  Structure and mechanism in protein science , 1998 .

[7]  Hanne Jarmer,et al.  Transcriptome analysis documents induced competence of Bacillus subtilis during nitrogen limiting conditions. , 2002, FEMS microbiology letters.

[8]  David Penny,et al.  Relics from the RNA World , 1998, Journal of Molecular Evolution.

[9]  S A Benner,et al.  Modern metabolism as a palimpsest of the RNA world. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[10]  H. White.  Coenzymes as fossils of an earlier metabolic state , 1976, Journal of Molecular Evolution.

[11]  R. Breaker,et al.  Immobilized RNA switches for the analysis of complex chemical and biological mixtures , 2001, Nature Biotechnology.

[12]  Evgeny Nudler,et al.  Sensing Small Molecules by Nascent RNA A Mechanism to Control Transcription in Bacteria , 2002, Cell.

[13]  T. Dafforn,et al.  Comprehensive biological catalysis , 1998 .

[14]  Ali Nahvi,et al.  Genetic control by a metabolite binding mRNA. , 2002, Chemistry & biology.

[15]  M Yarus,et al.  Diversity of oligonucleotide functions. , 1995, Annual review of biochemistry.

[16]  Ronald R. Breaker,et al.  Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression , 2002, Nature.

[17]  D. de Mendoza,et al.  Transcriptional Control of the Sulfur-RegulatedcysH Operon, Containing Genes Involved inl-Cysteine Biosynthesis in Bacillus subtilis , 2000, Journal of bacteriology.

[18]  T. Henkin,et al.  The S box regulon: a new global transcription termination control system for methionine and cysteine biosynthesis genes in Gram‐positive bacteria , 1998, Molecular microbiology.

[19]  J. Miranda-Ríos,et al.  A conserved RNA structure (thi box) is involved in regulation of thiamin biosynthetic gene expression in bacteria , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  T. Henkin.  Transcription termination control in bacteria. , 2000, Current opinion in microbiology.

[21]  R R Breaker,et al.  Relationship between internucleotide linkage geometry and the stability of RNA. , 1999, RNA.

[22]  T. Henkin,et al.  The T box and S box transcription termination control systems. , 2003, Frontiers in Bioscience.

[23]  G. F. Joyce.  The antiquity of RNA-based evolution , 2002, Nature.

[24]  P. Stragier,et al.  Plasmids for ectopic integration in Bacillus subtilis. , 1996, Gene.

[25]  R. Breaker,et al.  An mRNA structure that controls gene expression by binding FMN , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Nielsen.  A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes , 2022 .

[27]  T. Henkin,et al.  Transcription termination control of the S box system: Direct measurement of S-adenosylmethionine by the leader RNA , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Jeffrey E. Barrick,et al.  Metabolite-binding RNA domains are present in the genes of eukaryotes. , 2003, RNA.