DNA-directed RNA polymerase II subunit RPB1

POLR2A encodes the largest catalytic subunit of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase essential for synthesis of mRNA and non-coding RNAs. The protein forms the active catalytic center with subunit POLR2B and coordinates metal ions to catalyze phosphodiester bond formation during transcription initiation, elongation, and termination. Its unique C-terminal domain serves as a regulatory platform controlling transcription through phosphorylation, methylation, and acetylation modifications (UniProt: P24928).

POLR2A functions broadly across all gene expression pathways. UniProt disease associations include neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (NEDHIB, MIM 618603), reflecting the fundamental importance of transcriptional regulation in development.

In Alzheimer's disease, POLR2A is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.51 across examined subcellular fractions (Chaparral AD proteomics). This reduction in a core transcriptional machinery component may reflect broader dysregulation of gene expression patterns observed in AD pathology.