A, mRNAs enriched in RNF121 KO, with genes with pAdj<0.05 highlighted in blue. B, Ingenuity pathway analysis of AAV capsid binding partners in RNF121 KO cells showing pathways involved in RNA processes (green), translation (blue), viral infection (lime), DNA damage (purple), and miscellaneous (red). C, U2snRNP inhibitor PladB (20nM) treatment of Scr and RNF121 KO cells. D, DNA-PK inhibitor treatment of Scr and RNF121 KO cells (20uM). E, ATM/ATR Kinase inhibition of Scr and RNF121 KO cells (20uM). F, StringDB interactome of DNA damage and proteasomal machinery in RNF121 KO cells. G, Summary of findings highlighting VCP mediated transcriptional arrest in the absence of RNF121, an essential AAV host factor. A two-tailed unpaired t test was used unless otherwise indicated, with *, p<0.05; **, p<0.01; ***, p<0.005.