RNF12 catalyzes BRF1 ubiquitination and regulates RNA polymerase III-dependent transcription
RNF12 catalyzes BRF1 ubiquitination and regulates RNA polymerase III-dependent transcription
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RNF12 催化 BRF1 泛素化并调节 RNA 聚合酶 III 依赖性转录
DOI：
10.1074/jbc.ra118.004524
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发表时间：
2019-01-04
影响因子：
4.8
通讯作者：
Mei, Yide
中科院分区：
文献类型：
--
作者：
Wang, Fang;Zhao, Kailiang;Mei, Yide
RNA聚合酶III（Pol III）负责产生小的非编码RNA种类，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，但其潜在机制仍不清楚。已经证明TFIIIB的BRF 1亚基对于Pol III依赖性转录的准确起始是必不可少的。然而，目前尚不清楚BRF 1是否经历泛素修饰以及BRF 1泛素化是否调节Pol III依赖性转录。在这里，我们表明，RNF 12，一个RING结构域的泛素E3连接酶，物理相互作用与BRF 1。通过直接相互作用，RNF 12催化BRF 1的Lys（27）-和Lys（33）-连接的多泛素化。此外，RNF 12能够通过BRF 1负调节Pol III依赖性转录和细胞增殖。这些发现揭示了一种新的BRF 1调控机制，并揭示了RNF 12作为Pol III依赖性转录的重要调控因子。
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(27)- and Lys(33)-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.