8-oxoguanine riboswitches in bacteria detect and respond to oxidative DNA damage.
Siddhartha Hamal DhakalKumari KavitaShanker S S PanchapakesanAdam RothKimberly A HarrisPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
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.
Keyphrases
- gene expression
- nucleic acid
- genome wide
- dna damage
- dna methylation
- gold nanoparticles
- copy number
- sensitive detection
- induced apoptosis
- magnetic nanoparticles
- oxidative stress
- genome wide identification
- label free
- cell cycle arrest
- transcription factor
- cell free
- circulating tumor
- structure activity relationship
- cross sectional
- genome wide analysis
- dna binding
- bioinformatics analysis
- quantum dots
- pi k akt
- circulating tumor cells