Rrp8-flox Mouse

Rrp8, ribosomal RNA processing 8, is a nucleolar Rossman fold-like methyltransferase involved in RNA modification, specifically responsible for N1-methyladenosine (m1A) base modification at position 645 of 25S rRNA in yeast, corresponding to modifications in other species like Caenorhabditis elegans [3,4]. It has been associated with ribosomal biogenesis, including A2 cleavage and 40S biogenesis in yeast [4].

In hepatocellular carcinoma (HCC), Rrp8 is markedly overexpressed compared to adjacent normal tissues. Knockdown and knockout of Rrp8 in HCC cells attenuated cell proliferation and migration. Knockout also decreased the phosphorylation of MEK1/2 and β-catenin-(Y654) signalling pathway components, downregulated downstream effectors like Cyclin D1 and N-cadherin, and upregulated E-cadherin. Rrp8 is strongly associated with immune infiltration and various immune markers in HCC, and elevated expression indicates an unfavourable prognosis [1]. In podocytes, loss of Profilin1 led to downregulation of Rrp8, resulting in mitotic catastrophe. Overexpression of Rrp8 in Pfn1-KO podocytes partially rescued the phenotype in vitro [2].

In conclusion, Rrp8 plays a crucial role in RNA modification and ribosomal biogenesis. Its dysregulation is associated with diseases such as HCC and glomerular diseases. Studies using knockout models in these contexts have revealed its functions in cell proliferation, migration, and immune infiltration, providing potential therapeutic targets for these diseases.