POLR1C

POLR1C Full Name

polymerase (RNA) I polypeptide C, 30kDa

POLR1C Introduction

POLR1C is an essential, fundamentally conserved core structural subunit shared exclusively by two major eukaryotic transcription machineries: RNA polymerase I (Pol I) and RNA polymerase III (Pol III). In the nucleolus, the Pol I complex is exclusively dedicated to the massive transcription of the 45S ribosomal RNA (rRNA) precursor, while Pol III resides in the nucleoplasm transcribing small, essential non-coding RNAs such as tRNAs and the 5S rRNA. Because ribosomes are composed primarily of these highly specific rRNAs, POLR1C acts as an absolute master gatekeeper of ribosome biogenesis. By physically maintaining the stable assembly and catalytic function of both Pol I and Pol III, POLR1C dictates the entire translational capacity, protein synthesis rate, and ultimately, the survival and growth of the cell.

Figure 1. RNA Polymerase I subunits, rDNA repeat, and RNA Polymerase III subunits. (Source: Watt KE, et al. 2023)

Clinically, the profound developmental importance of POLR1C is starkly illustrated by its associated genetic syndromes. Biallelic and heterozygous mutations in the POLR1C gene are a major genetic cause of Treacher Collins syndrome (TCS) and a rare, severe form of hypomyelinating leukodystrophy. During early embryogenesis, neural crest cells—the highly migratory progenitors that form the facial bones and cartilage—are exceptionally sensitive to nucleolar stress. When POLR1C is mutated, rRNA synthesis drops significantly, inducing profound ribosomal stress. This specific stress triggers the massive stabilization and hyperactivation of the p53 tumor suppressor pathway, leading to the rapid, widespread apoptosis of these critical neural crest cells. Consequently, the embryological facial structures fail to develop properly, resulting in the severe craniofacial dysmorphisms (such as micrognathia and absent cheekbones) that are the clinical hallmark of Treacher Collins syndrome.

Alternate Names for POLR1C

POLR1C; polymerase (RNA) I polypeptide C, 30kDa; DNA-directed RNA polymerases I and III subunit RPAC1; RPA5; RPA39; RPA40; RPAC1; AC40; RPC40; RNA polymerases I and III subunit AC1

• 1. Watt KE, et al. RNA Polymerases I and III in development and disease. Semin Cell Dev Biol. 2023 Feb 28;136:49-63.
  2. Dauwerse JG, et al. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet. 2011 Jan;43(1):20-2.