Function
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[1].
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.
- M-box riboswitch couples Mg+2 level to expression of metal transport genes[2].
- YdaO riboswitch recognizes ATP[3].
- yybp-ykoy riboswitch recognizes Mn+2[4].
- PRPP riboswitch recognizes phosphoribosyl pyrophosphate[5].
For details on guanine riboswitch see
Structural highlights
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. The riboswitch-adenine complex shows the stacking interactions of the zippered-up junctional bubble which is formed by the adenine[6]. Water molecules are shown as red spheres.
3D structures of riboswitch
Riboswitch 3D structures
- ↑ Breaker, Ronald R. (28 March, 2008). Complex Riboswitches. Science, 319(5871), 1795-1797. doi:10.1126/science.1152621
- ↑ Ramesh A, Wakeman CA, Winkler WC. Insights into Metalloregulation by M-box Riboswitch RNAs via Structural Analysis of Manganese-Bound Complexes. J Mol Biol. 2011 Apr 8;407(4):556-70. Epub 2011 Feb 15. PMID:21315082 doi:10.1016/j.jmb.2011.01.049
- ↑ Watson PY, Fedor MJ. The ydaO motif is an ATP-sensing riboswitch in Bacillus subtilis. Nat Chem Biol. 2012 Dec;8(12):963-5. PMID:23086297 doi:10.1038/nchembio.1095
- ↑ Dambach M, Sandoval M, Updegrove TB, Anantharaman V, Aravind L, Waters LS, Storz G. The ubiquitous yybP-ykoY riboswitch is a manganese-responsive regulatory element. Mol Cell. 2015 Mar 19;57(6):1099-1109. PMID:25794618 doi:10.1016/j.molcel.2015.01.035
- ↑ Sherlock ME, Sudarsan N, Stav S, Breaker RR. Tandem riboswitches form a natural Boolean logic gate to control purine metabolism in bacteria. Elife. 2018 Mar 5;7:e33908. PMID:29504937 doi:10.7554/eLife.33908
- ↑ Serganov A, Yuan YR, Pikovskaya O, Polonskaia A, Malinina L, Phan AT, Hobartner C, Micura R, Breaker RR, Patel DJ. Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs. Chem Biol. 2004 Dec;11(12):1729-41. PMID:15610857 doi:S1074-5521(04)00343-6
