Structural basis for RNA polymerase III transcription repression by Maf1

Maf1 is a conserved inhibitor of RNA polymerase III (Pol III) that influences phenotypes ranging from metabolic efficiency to lifespan. Here, we present a 3.3-angstrom-resolution cryo-EM structure of yeast Maf1 bound to Pol III, establishing that Maf1 sequesters Pol III elements involved in transcription initiation and binds the mobile C34 winged helix 2 domain, sealing off the active site. The Maf1 binding site overlaps with that of TFIIIB in the preinitiation complex. A 3.3-angstrom-resolution cryo-EM structure of yeast Maf1 bound to RNA polymerase III (Pol III) explains the molecular mechanism for Pol III inhibition.