Journal
JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 12, Issue 2, Pages 113-124Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjz045
Keywords
RNF20; RNF40; gene transcription; p53; p21; PUMA
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Funding
- National Natural Science Foundation of China [31670812]
- grant for Returned Overseas Chinese Scholars of Hebei Province [CY201602]
- Hundreds of Outstanding Talent Innovation Projects in Hebei Province [SLRC2017023]
- Natural Science Foundation of Hebei Province [C2018201171]
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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.
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