Gene co-expression analysis of human RNASEH2A reveals functional networks associated with DNA replication, DNA damage response, and cell cycle regulation

Ribonuclease H2 (RNase H2) is a key enzyme for the removal of RNA found in DNA-RNA hybrids, playing a fundamental role in biological processes such as DNA replication, telomere maintenance and DNA damage repair. RNase H2 is a trimer composed of three subunits, being RNASEH2A the catalytic subunit. RNASEH2A expression levels have been shown to be upregulated in transformed and cancer cells. In this study we used a bioinformatics approach to identify RNASEH2A co-expressed genes in different human tissues to uncover biological processes in which RNASEH2A is involved. By implementing this approach, we identified functional networks for RNASEH2A that are not only involved in the processes of DNA replication and DNA damage response, but also in cell cycle regulation. Additional examination of protein-protein networks for RNASEH2A by the STRING database analysis, revealed a high co-expression correlation between RNASEH2A and the genes of the protein networks identified. Mass spectrometry analysis of RNASEH2A-bound proteins highlighted players functioning in cell cycle regulation. Further bioinformatics investigation showed increased gene expression of RNASEH2A in different types of actively cycling cells and tissues, and particularly in several cancers, supporting a biological role for RNASEH2A, but not the other two subunits of RNase H2, in cell proliferation.