Riboswitches – natural RNA sensors

By
Justyna Wojtczak
– June 1, 2011Posted in: Biochemistry
A guanine riboswitch complexed with the hypoxanthine, PDB: 1U8D
A guanine riboswitch complexed with the hypoxanthine (green ligand in center of the molecule), PDB: 1U8D

Riboswitches are RNA sensors, genetic regulatory elements found in the 5′ untranslated region of messenger RNA that act in the absence of protein cofactors.

They are residing in the 5′ untranslated regions (UTRs) of primarily prokaryotic mRNAs. Riboswitches complex folded structures that act as high affinity receptors for specific cellular metabolites. On metabolite binding they undergo conformational change, which modulates gene expression at posttranscriptional level, either through premature termination of transcription or inhibition of translation initiation.

They are composed of two structural domains: an aptamer domain and an expression platform. The aptamer domain binds the metabolite with high specificity resulting in the alteration of the RNA folding pattern mainly in the expression platform. The pink, orange and red parts, which are enclosing directly the ligand, are marked at the picture above.

Switching between two alternative RNA conformations, one of which is favoured in the absence of the bound metabolite and the other in its presence, leads to regulation of gene expression. The aptamer domain is highly conserved both at sequence as well as structure level among widely divergent organisms whereas the expression platform is highly variable even amongst the same riboswitch class. Riboswitches regulate genes in several metabolic pathways involved in the biosynthesis of vitamins, amino acids and purines.

Below are some anotation about knowned riboswitches:

Riboswitch name

 Location Metabolic pathway Structure and conservation

FMN, riboflavin, B2

 Are widely distributed across diverse bacterial species.
  • Riboflavin biosythesis and transport
  • This riboswitch class is characterized by the greatest degree of sequence conservation among members that are widely distributed across diverse bacterial species.
Cobalamin, B12 This riboswitch class is also widely distributed amongst bacterial genomes
  • Cobalamin synthesis and transport
  • Cobalt transport
  • Aerobic and anaerobic
  • ribonucleotide reductase
  • Glutamate fermentation
  • Succinate fermentation
  • It has the largest average length and shows poor sequence conservation.
TPP, B1 This is the most abundant riboswitch and is known to be present even in eukaryotes. This motif has been identified in most of the major bacterial taxonomic group
  • Thiamine synthesis, phosphorylation, and transport
  • It has intermediate level of sequence conservation.
  • Require Mg2+ for metabolite binding
Lysine A few bacterial groups, ex: Proteobacteria: Bacillales
  • Lysine sythesis and transport,
  • Lysine catabolism
  • The Lysine riboswitch shows low sequence conservation
  • Long aptemer sequence, motif called loop E
Glycine A few bacterial groups, ex: Proteobacteria:  

Bacillales
  • Glycine catabolism and efflux
  • Glycine riboswitch is the only known metabolite binding riboswitch that consists of two metabolite binding aptamer domains in tandem.
Purine The Purine riboswitch is found in few bacterial groups
  • Purine synthesis and transport
  • Purine riboswitch shows intermediate sequence conservation
  • Require Mg2+ for metabolite binding
Sam A few bacterial groups, ex: Proteobacteria: Bacillales
  • Methionine biosynthesis
  • Cysteine biosynthesis
  • Methionine recycling
  • Methylene tetrahydrafolate reductase
  • SAM synthesis
  • Metabolite transport
  • The Sam riboswitch shows high-level sequence conservation.
  • Complex tertiary structure involving at least five base-paired elements – RNA forms a pseudoknot between the hairpin loop of P2a and the junction between P3 and P4.
  • In addition, the bulge separating P2 from P2a appears to form a k-turn element
Sam alpha The Sam alpha riboswitch is found predominantly in alpha proteobacteria.
  • SAM binding
  • It is a short riboswitch with a relatively simple structure composed of a single hairpin
GlmS GlmS is found only in a few bacterial groups.
  • GlmS protein is an enzyme that catalyzes the conversion of fructose-6- phosphate to GlcN6P
  • Synthesis of GlcN6P
  • GlmS is the only known riboswitch to exhibit ribozyme activity.
  • It also shows high degree of sequence conservation
PreQ1 Batceria
  • precursor of queuine
  • PreQ1 has an unusually small aptamer domain with a simplified secondary structure consisting of a single stem loop structure.
  • The shortest known riboswitch (aptamer is an outlier with 34 nucleotides) that controls biosynthesis of the hypermodified nucleoside present in certain tRNAs

 

References:

  1. Riboswitch Detection Using Profile Hidden Markov Models – Payal Singh, Pradipta Bandyopadhyay1, Sudha Bhattacharya, A Krishnamachari and Supratim Sengupta, BMC Bioinformatics
  2. Structural features ofmetabolite-sensing riboswitches – Catherine A. Wakeman, Wade C. Winkler and Charles E. Dann III
  3. Regulation of Bacterial Gene Expression by Riboswitches Wade C.Winkler and Ronald R. Breaker
  4. The intricate world of riboswitches, Rebecca L Coppins1, Kathleen B Hall and Eduardo A Groisman
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More about Justyna Wojtczak
Written by: Justyna Wojtczak on June 1, 2011.
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