Rbm24, an RNA-binding protein and a target of p53, regulates p21 expression via mRNA stability.

The Journal of Biological Chemistry
Yuqian JiangXinbin Chen

Abstract

p21, a cyclin-dependent kinase inhibitor, is necessary for proper control of the cell cycle and premature senescence. Thus, p21 expression needs to be tightly controlled. In this study, we found that Rbm24, an RNA-binding protein and a target gene of the p53 protein, can regulate p21 expression via mRNA stability. Specifically, we showed that Rbm24 is induced by DNA damage and Mdm2 inhibitor Nutlin-3. We also found that p53 protein binds to and activates the promoter of the Rbm24 gene. Moreover, we found that overexpression of Rbm24 increases, whereas knockdown of Rbm24 decreases, p21 mRNA and protein expression. In addition, we demonstrated that overexpression of Rbm24 enhances the half-life of p21 transcript. Consistent with this, we provided evidence that Rbm24 binds to the 3'-untranslated region (3'-UTR) of p21 transcript and an AU/U-rich element in the p21 3'-UTR is necessary for Rbm24 to increase p21 expression. Finally, we showed that the RNA recognition motif in Rbm24 is required for binding to p21 transcript and subsequently for inducing p21 expression. Altogether, we uncovered that Rbm24 is a novel player in the p53 pathway, which may be explored to restore proper cell cycle control in p53-deficient tumors via p21.

References

Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·V DulićG H Stein
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·K CollinsN P Pavletich
Jul 8, 1999·Current Opinion in Cell Biology·A M Krecic, M S Swanson
Jan 11, 2000·Molecular and Cellular Biology·W WangM Gorospe
Dec 1, 2000·Nature·B VogelsteinA J Levine
Oct 31, 2003·Cancer Cell·John R JeffersGerard P Zambetti
Jan 6, 2004·Science·Lyubomir T VassilevEmily A Liu
Aug 3, 2004·Nature Medicine·Bert Vogelstein, Kenneth W Kinzler
Jun 3, 2008·Current Opinion in Structural Biology·Antoine CléryFrédéric H-T Allain
Dec 17, 2008·Current Molecular Medicine·Jin Zhang, Xinbin Chen
Oct 13, 2009·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Shoko MiyamotoTakayuki Morisaki
Jan 27, 2010·Cellular Signalling·Yong-Sam JungXinbin Chen
Jul 19, 2011·Genes & Development·Jin ZhangXinbin Chen
Oct 21, 2011·BMC Developmental Biology·Samantha MaraghAndrew S McCallion
Feb 22, 2012·Cardiovascular Research·Kar Lai PoonXiu Qin Xu
Jun 6, 2012·Comparative and Functional Genomics·Laurence Wurth

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Citations

Mar 24, 2016·Biomolecular NMR Assignments·Santosh Kumar Upadhyay, Cameron D Mackereth
Feb 17, 2015·Journal of Molecular and Cellular Cardiology·Cornelis J WeelandEsther E Creemers
Mar 4, 2017·Scientific Reports·Ishwarya Venkata NarayananMats Ljungman
Mar 30, 2017·The Journal of Biological Chemistry·Dominik PetersReiner U Jänicke
Jan 24, 2018·Cell Death and Differentiation·Min ZhangXinbin Chen
Aug 30, 2017·PloS One·Maarten M G van den HoogenhofEsther E Creemers
Dec 15, 2015·Experimental Dermatology·Eva Maria ValeskyMarkus Meissner
Aug 5, 2018·Scientific Reports·Maarten M G van den HoogenhofEsther E Creemers
Apr 14, 2019·Biomedicines·Lindy K BrastromDiane C Slusarski
Jul 10, 2020·Cellular and Molecular Life Sciences : CMLS·Cheng ZouDingxiao Zhang
Sep 20, 2020·Cells·Ji Hoon JungHua Lu
Aug 17, 2019·Cancers·Bahar Shamloo, Sinem Usluer
Nov 26, 2020·International Journal of Molecular Sciences·Shintaro MuraokaDaisuke Kaida
Jan 5, 2021·Frontiers in Cell and Developmental Biology·Yan ZhangZhigang Xu
Jan 21, 2021·International Journal of Molecular Sciences·Jin CaiNaihan Xu
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