RNA-directed off/on switch of RNase H activity using boronic ester formation. Issue 38 (19th September 2017)

• Record Type: Journal Article
• Authors: Reverte, Maëva; Barvik, Ivan; Vasseur, Jean-Jacques; Smietana, Michael
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 38(2017)
• Page Start: 8204
• Page End: 8210
• Publication Date: 2017-09-19
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob02145c
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A new concept to modulate RNase H activity is presented based on the boronic acid/boronate switch. Abstract : RNase H is a non-specific endonuclease which degrades selectively the RNA strand in DNA/RNA duplexes. We demonstrate in the present study that 5′-boronic acid modified oligonucleotides hybridized to a RNA target sequence converts RNase H to an inactivated enzyme complex. The dynamic formation of a boronate ester upon addition of a diol moiety disrupts the enzyme-inhibitor complex and reactivates RNase H. Moreover, we show that reactivation of RNase H function can also be engineered through short RNA trimers inputs that fashion RNase H from a non-specific DNA-guided enzyme into an informational and programmable RNA-guided one. Examples of programmable RNA recognition and cleavage illustrate the potential of this new stimuli-responsive system.