RNF12 catalyzes BRF1 ubiquitination and regulates RNA polymerase III–dependent transcription

RNA polymerase III (Pol III) is responsible for the production of small noncoding RNA species, including tRNAs and 5S rRNA. Pol III–dependent transcription is generally enhanced in transformed cells and tumors, but the underlying mechanisms remain not well-understood. It has been demonstrated that the BRF1 subunit of TFIIIB is essential for the accurate initiation of Pol III–dependent transcription. However, it is not known whether BRF1 undergoes ubiquitin modification and whether BRF1 ubiquitination regulates Pol III–dependent transcription. Here, we show that RNF12, a RING domain-containing ubiquitin E3 ligase, physically interacts with BRF1. Via direct interaction, RNF12 catalyzes Lys27- and Lys33-linked polyubiquitination of BRF1. Furthermore, RNF12 is able to negatively regulate Pol III–dependent transcription and cell proliferation via BRF1. These findings uncover a novel mechanism for the regulation of BRF1 and reveal RNF12 as an important regulator of Pol III–dependent transcription.