DNA-directed RNA polymerase I subunit A (POLR1A)

DNA-directed RNA polymerase I subunit A (POLR1A) is the largest and catalytic subunit of the multimeric RNA polymerase I enzyme complex, which is responsible for the transcription of rDNA into the 47S pre-ribosomal RNA precursor; this process is the first and key step in ribosome biogenesis in eukaryotic cells[1][2][3][4][5]. POLR1A, together with POLR1B/RPA2, forms the enzyme’s core catalytic site and orchestrates transcription initiation, elongation, and termination on ribosomal gene clusters. High POLR1A activity underpins ribosomal RNA synthesis required for cell growth and proliferation, and its dysregulation is linked to several cancers and genetic syndromes, such as Acrofacial dysostosis, Cincinnati type, or congenital leukodystrophies[1][2][3][4]. Pol I inhibitors are in development for oncology indications, targeting the abnormal transcriptional activity of this enzyme in tumor cells[2].

Other names

RPA1RNA polymerase I subunit ARNA polymerase I subunit A1RPA194DNA-directed RNA polymerase I largest subunitDNA-directed RNA polymerase I subunit RPA1A190DKFZP586M0122FLJ21915RPO1-4AFDCINHLD27RPA190RPO14polymerase (RNA) I subunit A

Inhibition of RNA polymerase I-mediated rRNA transcription; Induction of nucleolar stress leading to p53 activation