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Publication Abstract from PubMed

In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III transcription is observed in cancer and causative Pol III mutations have been described in neurodevelopmental disorders and hypersensitivity to viral infection. Here, we report a cryo-EM reconstruction at 4.0 A of human Pol III, allowing mapping and rationalization of reported genetic mutations. Mutations causing neurodevelopmental defects cluster in hotspots affecting Pol III stability and/or biogenesis, whereas mutations affecting viral sensing are located in proximity to DNA binding regions, suggesting an impairment of Pol III cytosolic viral DNA-sensing. Integrating x-ray crystallography and SAXS, we also describe the structure of the higher eukaryote specific RPC5 C-terminal extension. Surprisingly, experiments in living cells highlight a role for this module in the assembly and stability of human Pol III.

Structure of human RNA polymerase III.,Ramsay EP, Abascal-Palacios G, Daiss JL, King H, Gouge J, Pilsl M, Beuron F, Morris E, Gunkel P, Engel C, Vannini A Nat Commun. 2020 Dec 17;11(1):6409. doi: 10.1038/s41467-020-20262-5. PMID:33335104^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.