GPATCH4 functions as a regulator of nucleolar R-loops in hepatocellular carcinoma cells

Emerging evidence suggests that dysregulated RNA-binding proteins (RBPs) are associated a variety of cancers. However, the exact roles of RNA-binding proteins during the tumorigenesis of hepatocellular carcinoma (HCC) remain largely unknown. Here, we systematically searched for RBP candidates with potential oncogenic functions in HCC through multi-omics data integration strategies and identified that GPATCH4 gene is amplified and its high expression predicts a poor prognosis. We mapped the in vivo RNA binding sites of GPATCH4 by iCLIP-seq and characterized that GPATCH4 mainly bound rRNAs with a GC-rich consensus sequence. GPATCH4 promoted HCC cell proliferation and transformation both in vitro and in vivo through increasing rRNA transcription and global protein synthesis. In this study, we performed iCLIP-seq using Huh7 cells to characterize the RNA binding sites of GPATCH4.