DNA-directed RNA polymerase I subunit G (POLR1G)

DNA-directed RNA polymerase I subunit G (POLR1G) is an essential component of the RNA polymerase I (Pol I) complex, a multi-subunit DNA-dependent RNA polymerase responsible for the transcription of ribosomal RNA precursors in eukaryotes. POLR1G, also known as RPA34/PAF49/CD3EAP, forms part of the core enzyme that assembles in the nucleolus to synthesize the 45S pre-rRNA, which is subsequently processed into mature 18S, 5.8S, and 28S rRNAs, fueling ribosome biogenesis and thus protein synthesis. Proper POLR1G function is essential for cell growth and proliferation. Dysregulation of Pol I, including POLR1G, is associated with cancer and ribosomopathies, making Pol I a target for small-molecule inhibition to induce nucleolar stress and apoptosis in rapidly dividing tumor cells. While inhibitors exist for the Pol I complex, none directly and selectively target POLR1G. Safety challenges include effects on normal tissue regeneration and hematopoiesis due to the enzyme’s central role in ribosome production.

Other names

RPA34PAF49ASE1CASTCD3EAP (CD3E-associated protein)A34.5Antisense to ERCC-1 protein

Inhibition of rRNA synthesis by blocking Pol I activity Induction of nucleolar stress leading to p53-dependent apoptosis in rapidly dividing cells (notably in cancers) Selective disruption of ribosome biogenesis