POLR1A (D6S6S) Rabbit mAb #24799

RNA polymerase I (RNAPI) is a large multi-protein complex that functions as a DNA dependent, RNA polymerase, which is primarily responsible for the transcription of ribosomal RNA (rRNA) genes. The largest subunit, Rpa194, or POLR1A, along with selectivity factor 1 (SL1), and the transactivator protein upstream binding factor (UBF) make up the core transcriptional machinery of the RNAPI complex (1-3). The RNAPI complex is recruited specifically to rDNA promoters by SL1, which contains TBP and TAF proteins, to transcribe precursors to rRNA (2). These precursors are processed into 18S, 5.8S, and 28S mature rRNAs, which make up most of the ribosomal structure (1). Similar to the RNA polymerase II complex, there are other core components that are required for transcription of target genes such as the TFIIH complex and SPT6 (4, 5). Overexpression of nascent rRNA has been shown to be associated with poor prognosis in certain cancer types, and enlarged nucleoli are a hallmark of cellular proliferation and aggressive tumors (6-8). Oncogenes such as Myc, Ras, and PI3K can drive RNAPI-mediated rRNA transcription, making POLR1A a key therapeutic target (9). Indeed, specific targeting of RNAPI activity with a small molecule inhibitor can induce autophagy selectively in tumor cells while having minimal effects in normal cells (10). Additionally, mutations in POLR1A are associated with acrofacial dysostosis, Cincinnati type, a cranioskeletal malformation syndrome. Loss of function mutations result in disrupted ribosome biogenesis and p53-mediated cell death affecting skeletal precursor cells or the neural-crest (11).