POLR3A

POLR3A encodes the catalytic subunit A of RNA polymerase III (Pol III), also known as RPC1. This enzyme mediates transcription of small non-coding RNAs—including tRNAs, 5S rRNA, and U6 snRNA—critical for protein synthesis and pre-mRNA splicing. Its activity is tightly regulated by pathways like mTOR, linking cellular metabolism to transcriptional output.
Mutations in POLR3A cause POLR3-related leukodystrophy, a neurodegenerative disorder characterized by white matter abnormalities. Dysregulated Pol III (via POLR3A overexpression) also drives cancer progression in lung and colorectal tumors. Preclinical inhibitors like CX-5461, which targets Pol III, show anti-tumor efficacy, with ongoing efforts to translate these into clinical therapies.