Open AccessThe RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing
Author(s) -
Chen Wu,
Yaqi Cui,
Xiuhua Li,
Feng Zhang,
Lin-Yu Lu,
Xiaochun Yu
Publication year - 2019
Publication title -
journal of molecular cell biology/journal of molecular cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.825
H-Index - 62
eISSN - 1674-2788
pISSN - 1759-4685
DOI - 10.1093/jmcb/mjz045
Subject(s) - rna splicing , histone h2b , microbiology and biotechnology , biology , chromatin , spliceosome , transcription factor , rna polymerase ii , puma , chromatin remodeling , transcription (linguistics) , gene , genetics , gene expression , promoter , rna , linguistics , philosophy
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.