Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs

Alexander Serganov, Yu Ren Yuan, Olga Pikovskaya, Anna Polonskaia, Lucy Malinina, Anh Tuân Phan, Claudia Hobartner, Ronald Micura, Ronald R. Breaker, Dinshaw J. Patel

Research output: Contribution to journalArticlepeer-review

406 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1729-1741
Number of pages13
JournalChemistry and Biology
Volume11
Issue number12
DOIs
StatePublished - Dec 2004

Bibliographical note

Funding Information:
This research was supported by National Institutes of Health grant GM73618, the DeWitt Wallace Foundation, and the Abby Rockefeller Mauze Trust to D.J.P., National Institutes of Health grant GM068819 and National Science Foundation grant EIA-0323510 to R.R.B., and the Austrian Science Fund (FWF) to R.M. We thank A. Teplov for help with data collection, and M. Becker and the staff of the X25 and X12C beam lines at the National Synchrotron Light Source for assistance with data collection. D.J.P. is a member of the New York Structural Biology Center, which is supported by National Institutes of Health grant GM66354.

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