RNPC1 modulates the RNA-binding activity of, and cooperates with, HuR to regulate p21 mRNA stability.
RNPC1 modulates the RNA-binding activity of, and cooperates with, HuR to regulate p21 mRNA stability.
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DOI：
10.1093/nar/gkp1229
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发表时间：
2010-04
影响因子：
14.9
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Cho SJ;Zhang J;Chen X
P21是一种细胞周期蛋白依赖性激酶抑制剂，在应激刺激下细胞周期的调节中起着关键作用。P21的表达通过转录、转录后和翻译后机制高度调节。以前，我们和其他人表明，p21的表达是通过p21 mRNA的稳定性调节RNPC 1，p53家族的目标和HuR，ELAV家族RNA结合蛋白的成员。HuR携带三个高度保守的RNA识别基序（RRM），而RNPC 1携带一个。我们发现RNPC 1调节p21 mRNA稳定性的能力依赖于HuR。我们还发现RNPC 1和HuR之间存在物理相互作用，RNPC 1中的RRM结构域和HuR中的RRM 3是它们相互作用所必需的。有趣的是，我们发现RNPC 1和HuR都可以结合p21 3′-UTR中的富含AU的元件（战神），它们分别优先结合上游和下游战神。最后，我们发现RNPC 1在体外和体内都能增强HuR与p21转录本的RNA结合活性。总之，我们假设RNPC 1调节RNA结合活性，并与HuR合作，调节p21 mRNA的稳定性。
P21, a cyclin-dependent kinase inhibitor, plays a pivotal role in the cell-cycle regulation in response to stress stimuli. P21 expression is highly regulated through transcriptional, post-transcriptional and post-translational mechanisms. Previously, we and others showed that p21 expression is regulated through p21 mRNA stability by RNPC1, a target of the p53 family and HuR, a member of the ELAV family RNA-binding proteins. HuR carries three highly conserved RNA recognition motifs (RRMs) whereas RNPC1 carries one. Here we found that the ability of RNPC1 to regulate p21 mRNA stability is dependent on HuR. We also found that RNPC1 and HuR physically interact, and the RRM domain in RNPC1 and RRM3 in HuR are necessary for their interaction. Interestingly, we found that RNPC1 and HuR, both of which can bind AU-rich elements (AREs) in p21 3′-UTR, preferentially bind the upstream and downstream AREs, respectively. Finally, we showed that the RNA-binding activity of HuR to p21 transcript was enhanced by RNPC1 in vitro and in vivo. Together, we hypothesize that RNPC1 modulates the RNA-binding activity of, and cooperates with, HuR to regulate p21 mRNA stability.
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