Target intelligence / Profile preview

Ribonuclease H1 (RNase H1)

Target
RNase H1
Molecular classification
Enzyme, Endonuclease, Ribonuclease
01

Overview

Ribonuclease H1 (RNase H1) is a non-sequence-specific endonuclease enzyme found in prokaryotes and eukaryotes, encoded in humans by the RNASEH1 gene. It specifically cleaves the RNA strand of RNA/DNA hybrids through a hydrolytic mechanism, playing a crucial role in the removal of RNA from such hybrids, most notably in the context of R-loop structures that form during transcription and replication. RNase H1 maintains genome stability by preventing the accumulation of these hybrids, which can otherwise lead to genomic instability. Structurally, the enzyme contains a characteristic DEDD active site motif, requiring magnesium ions for catalysis. Its activity has been harnessed therapeutically, particularly in antisense oligonucleotide (ASO) therapies targeting disease-associated RNA. RNase H1 dysfunction is associated with impaired DNA repair, increased R-loop formation, and is implicated as a regulatory factor in some cancer types[1][2][3][5][8].

Other names
RNH1RNASEH1RNHRibonuclease H (when referring to type 1)ribonuclease HI (in prokaryotes)
02

Mechanism of action

Hydrolytic cleavage of RNA in RNA/DNA duplexes Removal of RNA from RNA-DNA hybrids formed during DNA replication, repair, and transcription

03

Biological functions

Genome stability maintenanceCleavage of RNA in RNA/DNA hybridsHybrid removal (particularly R-loops)RNA polymerase II transcription termination
04

Disease associations

Cancer (potential regulator in tumor biology)Neurodegenerative disease (implied by genome instability, but no direct strong evidence in search results)Other (genetic diseases related to DNA repair, implied)
05

Safety considerations

Essential for genome stability; inhibition could cause DNA damage and compromised cellular functionPotential for off-target effects when recruiting RNase H1 for antisense oligonucleotide (ASO) therapy
06

Interacting drugs

Antisense oligonucleotides (therapeutics designed to recruit or activate RNase H1 to degrade target RNA, e.g., as used in some ASO therapies)
07

Biomarkers

Accumulation of RNA/DNA hybrids (R-loops) as a potential biomarker of RNase H1 deficiencyExpression level of RNASEH1 mRNA or protein

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