RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript.

p21, a cyclin-dependent kinase inhibitor, is transcriptionally regulated by the p53 family to induce cell cycle arrest. p21 is also regulated post-transcriptionally upon DNA damage in a p53-dependent manner, but the mechanism is uncertain. Here, we found that RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript. Specifically, we showed that RNPC1 is induced by the p53 family and DNA damage in a p53-dependent manner. The RNPC1 gene encodes at least two alternative spliced isoforms, RNPC1a and RNPC1b, both of which contain an intact RNA recognition motif. Interestingly, we found that RNPC1a, but not RNPC1b, induces cell cycle arrest in G1, although both isoforms are expressed in the nucleus and cytoplasm. In addition, we found that while both isoforms directly bind to the 3' untranslated region in p21 transcript, only RNPC1a is able to stabilize both the basal and stress-induced p21 transcripts. Conversely, RNPC1a knockdown destabilizes p21 transcript. Finally, we found that RNPC1a is required to maintain the stability of p21 transcript induced by p53.