Affiliation:
1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511-8103
2. HHMI, Yale University, New Haven, CT 06511-8103
3. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511-8103
Abstract
Riboswitches rely on structured aptamer domains to selectively sense their target ligands and regulate gene expression. However, some riboswitch aptamers in bacteria carry mutations in their otherwise strictly conserved binding pockets that change ligand specificities. The aptamer domain of a riboswitch class originally found to selectively sense guanine forms a three-stem junction that has since been observed to exploit numerous alterations in its ligand-binding pocket. These rare variants have modified their ligand specificities to sense other purines or purine derivatives, including adenine, 2′-deoxyguanosine (three classes), and xanthine. Herein, we report the characteristics of a rare variant that is narrowly distributed in the
Paenibacillaceae
family of bacteria. Known representatives are always associated with genes encoding 8-oxoguanine deaminase. As predicted from this gene association, these variant riboswitches tightly bind 8-oxoguanine (8-oxoG), strongly discriminate against other purine derivatives, and function as genetic “ON” switches. Following exposure of cells to certain oxidative stresses, a representative 8-oxoG riboswitch activates gene expression, likely caused by the accumulation of 8-oxoG due to oxidative damage to G nucleobases in DNA, RNA, and the nucleotide pool. Furthermore, an engineered version of the variant aptamer was prepared that exhibits specificity for 8-oxoadenine, further demonstrating that RNA aptamers can acquire mutations that expand their ability to detect and respond to oxidative damage.
Funder
HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
HHS | NIH | National Institute of General Medical Sciences
Howard Hughes Medical Institute
Publisher
Proceedings of the National Academy of Sciences