The RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing
The RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing
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RNF20/40 复合物调节 p53 依赖性基因转录和 mRNA 剪接
DOI：
10.1093/jmcb/mjz045
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发表时间：
2020
影响因子：
5.5
通讯作者：
Yu Xiaochun
中科院分区：
文献类型：
--
作者：
Wu Chen;Cui Yaqi;Liu Xiuhua;Zhang Feng;Lu Lin-Yu;Yu Xiaochun
摘要p53是调控基因转录的关键转录因子。然而，染色质相关的p53基因转录的分子机制仍然是难以捉摸的。在这里，使用无偏蛋白亲和纯化，我们发现RNF 20/40复合物与染色质上的p53相关。进一步的分析表明，p53介导RNF 20/40复合物募集到p53靶基因位点，包括p21和p53靶基因位点，并通过RNF 20/40复合物依赖的组蛋白H2 B泛素化（ubH 2B）调节p21和p53靶基因位点的转录。缺乏RNF 20/40复合物不仅抑制ubH 2B，而且抑制p21和cDNAA成熟mRNA的产生。此外，ubH 2B被前mRNA加工剪接因子8（PRPF 8）的泛素结合基序识别，PRPF 8是剪接体中的一个亚基，并且PRPF 8是p21和p53 A的mRNA成熟所必需的。我们的研究揭示了一种新的p53依赖性途径，调节mRNA剪接抑制肿瘤。
Abstract p53 is a key transcription factor to regulate gene transcription. However, the molecular mechanism of chromatin-associated p53 on gene transcription remains elusive. Here, using unbiased protein affinity purification, we found that the RNF20/40 complex associated with p53 on the chromatin. Further analyses indicated that p53 mediated the recruitment of the RNF20/40 complex to p53 target gene loci including p21 and PUMA loci and regulated the transcription of p21 and PUMA via the RNF20/40 complex-dependent histone H2B ubiquitination (ubH2B). Lacking the RNF20/40 complex suppressed not only ubH2B but also the generation of the mature mRNA of p21 and PUMA. Moreover, ubH2B was recognized by the ubiquitin-binding motif of pre-mRNA processing splicing factor 8 (PRPF8), a subunit in the spliceosome, and PRPF8 was required for the maturation of the mRNA of p21 and PUMA. Our study unveils a novel p53-dependent pathway that regulates mRNA splicing for tumor suppression.