Transcriptional changes by RBN-2397 treatment and FRA1 knockdown in NCI-H1975 cells

PARP7 inhibitors reduce tumor growth in a cell-autonomous manner and by enhancing immune recognition through restoring nucleic acid (NA)-sensing-dependent innate immune signaling. However, the molecular targets of PARP7-mediated ADP-ribosylation, regulating cell survival and innate immune signaling, remained elusive. Here, we identified PARP7 as a nuclear and cysteine-specific mono-ART that ADP-ribosylates proteins critical for regulating gene expression, such as the AP-1 transcription factor FRA1. Upon PARP7 inhibition the loss of FRA1 ADP-ribosylation increased FRA1 degradation in a PSMC3 and proteasomal-dependent manner. To further investigate how FRA1 promotes cell survival, we investigated transcriptional changes after RBN-2397 treatment and FRA1 knockdown in the PARP7 inhibitor sensitive cell line NCI-H1975 by RNA sequencing. Overall design: RNA sequencing of NCI-H1975 cells after RBN-2397 treatment (6h) or FRA1 knockdown (48h)