Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs.
Metabolite-sensing mRNAs, or "riboswitches," specifically interact with small ligands and direct expression of the genes involved in their metabolism. Riboswitches contain sensing "aptamer" modules, capable of ligand-induced structural changes, and downstream regions, harboring expression-controlling elements. We report the crystal structures of the add A-riboswitch and xpt G-riboswitch aptamer modules that distinguish between bound adenine and guanine with exquisite specificity and modulate expression of two different sets of genes. The riboswitches form tuning fork-like architectures, in which the prongs are held in parallel through hairpin loop interactions, and the internal bubble zippers up to form the purine binding pocket. The bound purines are held by hydrogen bonding interactions involving conserved nucleotides along their entire periphery. Recognition specificity is associated with Watson-Crick pairing of the encapsulated adenine and guanine ligands with uridine and cytosine, respectively.
Serganov
Alexander
A
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Yuan
Yu-Ren
YR
Pikovskaya
Olga
O
Polonskaia
Anna
A
Malinina
Lucy
L
Phan
Anh Tuân
AT
Hobartner
Claudia
C
Micura
Ronald
R
Breaker
Ronald R
RR
Patel
Dinshaw J
DJ
D000225:Adenine / Q000737:chemistry* / Q000378:metabolism; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006147:Guanine / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012680:Sensitivity and Specificity; D013379:Substrate Specificity; D041261:Vibrio vulnificus / Q000235:genetics / Q000378:metabolism
D008024:Ligands; D012329:RNA, Bacterial; D012333:RNA, Messenger; D006147:Guanine; D000225:Adenine