Arginine methylation-mediated FXR1-G4 RNA binding in cancer cells
The RBP, FXR1, is overexpressed in many epithelial tumors containing a canonical RGG box domain. FXR1 controls post-transcriptional gene regulation through changes in mRNA turnover and translation of target genes. Here we show that arginine methyltransferase PRMT5- mediated specific arginine methylation of FXR1 increases its stability in cancer cells. FXR1-dependent gene signatures show decreased expression and instability of G4-rich sequences containing mRNAs such as CDKN1A, PLK2, TCN2, and TRAF4. Furthermore, structural features of FXR1 and G4-RNA interactions provide novel insights into the critical arginine amino acids of FXR1 essential for G4-RNA-binding and turnover activity. In addition, analysis of the eCLIP data provides various RNA targets and the G-rich sequence motifs of FXR1 in head and neck cancer cell line. Thus, our results indicate that PRMT5-mediated methylation of FXR1 binding with G4-RNAs favors mRNA stability and turnover, contributing to cancer cell growth and proliferation. Overall design: To Investigate the post-transcriptional regulation of FXR1, we used 74B head and neck cancer cell lines and UV irradited them to identify the FXR1 interacting RNA sequences.