The catalytic mechanism, metal dependence, substrate specificity, and biodiversity of ribonuclease H.

Abstract

Ribonucleoside monophosphates are inevitably misincorporated into the DNA genome inside cells, and they need to be excised to avoid chromosome instability. Ribonucleases H (RNases H) are enzymes that specifically hydrolyze the RNA strand of RNA/DNA hybrids or the RNA moiety from DNA containing a stretch of RNA, they therefore are required for DNA integrity. Extensive studies have drawn a mostly clear picture of the mechanisms of RNase H catalysis, but some questions are still lacking definitive answers. This review summarizes three alternative models of RNase H catalysis. The two-metal model is prevalent, but a three-metal model suggests the involvement of a third cation in catalysis. Apparently, the mechanisms underlying metal-dependent hydrolyzation are more complicated than initially thought. We also discuss the metal choices of RNases H and analyze how chemically similar cations function differently. Substrate and cleavage-site specificities vary among RNases H, and this is explicated in detail. An intriguing phenomenon is that organisms have diverse RNase H combinations, which may provide important hints to how rnh genes were transferred during evolution. Whether RNase H is essential for cellular growth, a key question in the study of in vivo functions, is also discussed. This article may aid in understanding the mechanisms underlying RNase H and in developing potentially promising applications of it.