Ribonuclease HI (RNase HI)

Ribonuclease HI (RNase HI) is a critical endoribonuclease enzyme responsible for identifying and cleaving the RNA strand within RNA/DNA heteroduplexes. It plays a fundamental role in maintaining genomic integrity by resolving R-loops—structures that form when RNA displaces DNA in a helix—and by processing Okazaki fragment primers during DNA replication. In the field of biotechnology, RNase HI has emerged as a promising therapeutic target for the selective elimination of antibiotic-resistant bacteria, as its inhibition causes a lethal accumulation of DNA damage in specific resistant strains. Furthermore, the RNase H domain of viral reverse transcriptases, notably in HIV, is a validated target for the development of antiretroviral drugs. While the term 'HI splitting' is not a canonical pharmacological name, it descriptively refers to the enzyme's primary biochemical function of splitting or cleaving the RNA portion of hybrid nucleic acid substrates. It should also be distinguished from the 'Hi splitting' algorithm used in machine learning for hit identification benchmarking in drug discovery, which is a data science methodology rather than a biological target.

Other names

RNase HIRibonuclease H type 1RNH1RNA-DNA hybrid-specific ribonuclease

Inhibits the hydrolytic cleavage of RNA/DNA heteroduplexes, leading to the lethal accumulation of R-loops and subsequent double-strand DNA breaks.