RNF12 催化 BRF1 的泛素化，调节 RNA 聚合酶 III 依赖的转录。
RNF12 catalyzes BRF1 ubiquitination and regulates RNA polymerase III-dependent transcription.
机构信息
Anhui Province Key Laboratory of Medical Physics and Technology/Center of Medical Physics and Technology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, Hefei 230031, Anhui, China; Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230026, Anhui, China.
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230026, Anhui, China.
出版信息
J Biol Chem. 2019 Jan 4;294(1):130-141. doi: 10.1074/jbc.RA118.004524. Epub 2018 Nov 9.
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 Lys- and Lys-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.
RNA 聚合酶 III（Pol III）负责产生小非编码 RNA 物种，包括 tRNA 和 5S rRNA。Pol III 依赖性转录通常在转化细胞和肿瘤中增强，但潜在的机制仍未得到很好的理解。已经证明，TFIIIB 的 BRF1 亚基对于 Pol III 依赖性转录的准确起始是必不可少的。然而，尚不清楚 BRF1 是否经历泛素修饰，以及 BRF1 泛素化是否调节 Pol III 依赖性转录。在这里，我们表明，RNF12，一种含有 RING 结构域的泛素 E3 连接酶，与 BRF1 发生物理相互作用。通过直接相互作用，RNF12 催化 BRF1 的 Lys 和 Lys 连接多泛素化。此外，RNF12 能够通过 BRF1 负调控 Pol III 依赖性转录和细胞增殖。这些发现揭示了 BRF1 调节的新机制，并揭示了 RNF12 是 Pol III 依赖性转录的重要调节剂。
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