Riboswitch

Normally, a variety of proteins and protein cofactors control gene expression in an organism by binding to different sites on messenger RNA (mRNA). Riboswitches are genetic regulatory elements that are built directly into the RNA. They are a type of noncoding RNA that regulate gene expression in the absence of proteins by switching from one structural conformation (shape) to another in response to ligand binding. Most contain a single binding site that recognizes a specific ligand. The ability of a riboswitch to discriminate against molecules that are similar or closely related to its ligand is essential to prevent metabolic misregulation.

The various classes of riboswitches discovered so far are differentiated by their respective ligands. Every class of riboswitch is characterized by an aptamer (binding site) domain, which provides the site for ligand binding, and an expression platform that undergoes conformational change. The sequences and structures of aptamer domains are highly conserved, and therefore exhibit little variation among riboswitches belonging to the same class. Atomic-resolution structures of riboswitch binding sites show that they make numerous hydrogen bonds with their ligands, forming contacts that stabilize RNA interactions to further increase affinity. Some binding sites form pockets that entirely engulf the ligand, and in these instances an induced-fit mechanism of binding must occur. For details on guanine riboswitch see Guanine-Binding Riboswitch and Guanine riboswitch.

3D structures of riboswitch3D structures of riboswitch

Adenine riboswitchAdenine riboswitch

1y26 – AR + adenine – Vibrio vulnificus
3ivn – BsAR (mutant) – Bacillus subtilis
3la5 - BsAR (mutant) + azacytosine

Guanine riboswitchGuanine riboswitch

1y27 – BsGR residues 185-252 + guanine
2g9c, 3fo4, 3fo6, 3ges, 3gog, 3rkf - BsGR (mutant) + guanine derivative
3got - BsGR (mutant) + adenine derivative
2xo1 - BsGR aptamer domain + adenine derivative
3g4m, 3ger - BsGR + guanine derivative
2xnz - BsGR aptamer domain + guanine derivative
2xo0 - BsGR aptamer domain + triazine derivative
2ees, 2eet, 2eeu, 2eev, 2eew - BsGR (mutant) + hypoxanthine
3gao - BsGR + xanthine
2xnw – BsGR + Mn

Thiamine pyrophosphate riboswitchThiamine pyrophosphate riboswitch

2gdi – TPPR + TPP – synthetic
2hoj, 2hok, 2hol – EcTPPR + TPP + metal ion – Escherichia coli
2hom – EcTPPR + TMP
2hoo, 2hop – EcTPPR + TPP analog
3d2g, 3d2v, 3d2x - TPPR + TPP analog – Arabidopsis thaliana

S-adenosylmethionine riboswitchS-adenosylmethionine riboswitch

2gis – TtSAMR + SAM – Thermoanaerobacter tengcongensis
3iqr, 2ydh, 2ygh - TtSAMR (mutant) + SAM
3iqp - TtSAMR
2qwy, 3e5c, 3e5e, 3e5f, 3iqn - SAMR + SAM – synthetic

S-adenosylhomocysteine riboswitchS-adenosylhomocysteine riboswitch

3npn, 3npq – SAHR + SAH – Ralstonia solanacearum

Lysine riboswitchLysine riboswitch

3d0u – KR ligand-binding domain + Lysine – Thermotoga maritima

FMN riboswitchFMN riboswitch

3f2q, 3f2t, 3f2w, 3f2x, 3f2y, 3f30, 3f4e – FnFMNR + FMN – Fusobacterium nucleatum
2yie - FnFMNR aptamer domain + FMN
3f4g, 3f4h – FnFMNR + flavin derivative
2yif - FnFMNR + GTP

Pre-queosine riboswitchPre-queosine riboswitch

3fu2, 3k1v – BsQ1R + queosine
3gca – TtQ0R + queosine
3q50, 3q51 – TtQ1R aptamer domain + queosine

C-di-GMP riboswitchC-di-GMP riboswitch

3irw, 3mxh – VcGMPR + C-di-GMP + GTP + U1 small nuclear ribonucleoprotein – Vibrio cholerae
3iwn – VcGMPR + C-di-GMP + U1 small nuclear ribonucleoprotein
3mum, 3mur, 3mut - VcGMPR (mutant) + C-di-GMP + U1 small nuclear ribonucleoprotein
3muv - VcGMPR (mutant) + C-di-AMP + U1 small nuclear ribonucleoprotein
3q3z - GMPR + C-di-GMP – Clostridium acetobutylicum

Glycine riboswitchGlycine riboswitch

3owi, 3oww, 3owz – VcGlyR + glycine
3ox0, 3oxe, 3oxj, 3oxm – VcGlyR + GDP + cytidine cyclic phosphate
3oxb, 3oxd – VcGlyR (mutant) + GDP + cytidine cyclic phosphate
3p49 – FnGlyR + U1 small nuclear ribonucleoprotein + glycine

M-Box riboswitchM-Box riboswitch

3pdr – BsMBR + Mn

Tetrahydrofolate riboswitchTetrahydrofolate riboswitch

3suh, 3sux – EsTHFR + THF derivative – Eubacterium siraeum
3suy - EsTHFR + cytidine cyclic phosphate
3sd1 – THFR + pteridine derivative – synthetic
3sd3 – THFR (mutant) + pteridine derivative – synthetic