Rnaseh2a, Ribonuclease H2, subunit A, is a key component of the RNASEH2 endonuclease complex. RNaseH2 functions to remove ribonucleoside monophosphates (rNMPs) from the genome, which is essential for genome stability [2]. It is involved in pathways related to nucleic acid metabolism and sensing, and its malfunction can have significant biological consequences. Genetic models, such as knockout zebrafish, are valuable for studying its functions [3].

Mutations in Rnaseh2a are associated with Aicardi-Goutières syndrome, an inflammatory disease. In a study of 374 patients with mutations in genes related to this syndrome, those with Rnaseh2a mutations contributed to the overall phenotypes, which included in utero or post-natal onset encephalopathy, loss of skills, and other distinct phenotypes like bilateral striatal necrosis [1]. In zebrafish, while first-generation Rnaseh2a knockouts showed little phenotypic abnormality, second-generation offspring had reduced development, increased ribonucleotide incorporation, upregulation of inflammatory markers, and embryonic lethality, suggesting compensatory mechanisms in the first-generation and ribodysgenesis causing lethality in the second-generation [3].

In conclusion, Rnaseh2a is crucial for maintaining genome stability by removing rNMPs from the genome. Studies using knockout models, like the zebrafish, have revealed its role in preventing phenotypes associated with Aicardi-Goutières syndrome. Understanding Rnaseh2a function provides insights into the disease mechanisms and may guide the development of treatment strategies for this and potentially related disorders.