Pre-mRNA processing factor 19 (PRPF19)

Pre-mRNA processing factor 19 (PRPF19) is a highly conserved E3 ubiquitin ligase that serves as a central scaffold and enzymatic component of the spliceosome, required for pre-mRNA splicing and the DNA damage response. As a core constituent of the PRP19 complex/Nineteen complex (NTC), PRPF19 is essential for spliceosome assembly, catalysis, and remodeling; it mediates Lys-63–linked polyubiquitination of spliceosomal proteins, facilitating snRNP complex transitions. PRPF19 is also directly implicated in DNA double-strand break repair, where it targets RPA1 and RPA2 for ubiquitination, activating ATR-dependent signaling. It has further roles in transcription-coupled repair, protein degradation, cell proliferation, apoptosis suppression, and potentially neural development and lipid droplet biogenesis. PRPF19’s dysfunction or aberrant regulation is linked to cancer and other diseases, making it a subject of therapeutic research, yet targeting it poses significant challenges due to its fundamental roles in cell function

Other names

PRP19PSO4hPrp19Nuclear matrix protein 42 (NMP42)

For investigational approaches: inhibition or modulation of spliceosome assembly or ubiquitin ligase activity to impact RNA processing, DNA repair, and apoptosis, particularly in oncology