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The RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing
Chen Wu 1,2,† , Yaqi Cui 1,2,† , Xiuhua Liu1, Feng Zhang3, Lin-Yu Lu 4,5 , and Xiaochun Yu 2,*
1 College of Life Sciences, Hebei University, Baoding 071000, China
2 Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
3 College of Life and Environment Sciences, Shanghai Normal University, Shanghai, China
4 Key Laboratory of Reproductive Genetics, Ministry of Education and Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
5 Institute of Translational Medicine, Zhejiang University, Hangzhou, China
† These authors contributed equally to this work.
*Correspondence to:Xiaochun Yu, E-mail: xyu@coh.org
J Mol Cell Biol, Volume 12, Issue 2, February 2020, 113-124,  https://doi.org/10.1093/jmcb/mjz045
Keyword: RNF20, RNF40, gene transcription, p53, p21, PUMA

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.


Volume 12, Issue 2
February 2020