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Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines

The X chromosome-linked inhibitor of apoptosis protein (XIAP) is the most potent intrinsic caspase inhibitor and plays an important role in the maintenance of intestinal epithelial integrity. The RNA binding protein, HuR, regulates the stability and translation of many target transcripts. Here, we r...

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Autores principales: Zhang, Xian, Zou, Tongtong, Rao, Jaladanki N., Liu, Lan, Xiao, Lan, Wang, Peng-Yuan, Cui, Yu-Hong, Gorospe, Myriam, Wang, Jian-Ying
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2009
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794158/
https://www.ncbi.nlm.nih.gov/pubmed/19825980
http://dx.doi.org/10.1093/nar/gkp755
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author Zhang, Xian
Zou, Tongtong
Rao, Jaladanki N.
Liu, Lan
Xiao, Lan
Wang, Peng-Yuan
Cui, Yu-Hong
Gorospe, Myriam
Wang, Jian-Ying
author_facet Zhang, Xian
Zou, Tongtong
Rao, Jaladanki N.
Liu, Lan
Xiao, Lan
Wang, Peng-Yuan
Cui, Yu-Hong
Gorospe, Myriam
Wang, Jian-Ying
author_sort Zhang, Xian
collection PubMed
description The X chromosome-linked inhibitor of apoptosis protein (XIAP) is the most potent intrinsic caspase inhibitor and plays an important role in the maintenance of intestinal epithelial integrity. The RNA binding protein, HuR, regulates the stability and translation of many target transcripts. Here, we report that HuR associated with both the 3′-untranslated region and coding sequence of the mRNA encoding XIAP, stabilized the XIAP transcript and elevated its expression in intestinal epithelial cells. Ectopic HuR overexpression or elevated cytoplasmic levels of endogenous HuR by decreasing cellular polyamines increased [HuR/XIAP mRNA] complexes, in turn promoting XIAP mRNA stability and increasing XIAP protein abundance. Conversely, HuR silencing in normal and polyamine-deficient cells rendered the XIAP mRNA unstable, thus reducing the steady state levels of XIAP. Inhibition of XIAP expression by XIAP silencing or by HuR silencing reversed the resistance of polyamine-deficient cells to apoptosis. Our findings demonstrate that HuR regulates XIAP expression by stabilizing its mRNA and implicates HuR-mediated XIAP in the control of intestinal epithelial apoptosis.
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spelling pubmed-27941582009-12-16 Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines Zhang, Xian Zou, Tongtong Rao, Jaladanki N. Liu, Lan Xiao, Lan Wang, Peng-Yuan Cui, Yu-Hong Gorospe, Myriam Wang, Jian-Ying Nucleic Acids Res RNA The X chromosome-linked inhibitor of apoptosis protein (XIAP) is the most potent intrinsic caspase inhibitor and plays an important role in the maintenance of intestinal epithelial integrity. The RNA binding protein, HuR, regulates the stability and translation of many target transcripts. Here, we report that HuR associated with both the 3′-untranslated region and coding sequence of the mRNA encoding XIAP, stabilized the XIAP transcript and elevated its expression in intestinal epithelial cells. Ectopic HuR overexpression or elevated cytoplasmic levels of endogenous HuR by decreasing cellular polyamines increased [HuR/XIAP mRNA] complexes, in turn promoting XIAP mRNA stability and increasing XIAP protein abundance. Conversely, HuR silencing in normal and polyamine-deficient cells rendered the XIAP mRNA unstable, thus reducing the steady state levels of XIAP. Inhibition of XIAP expression by XIAP silencing or by HuR silencing reversed the resistance of polyamine-deficient cells to apoptosis. Our findings demonstrate that HuR regulates XIAP expression by stabilizing its mRNA and implicates HuR-mediated XIAP in the control of intestinal epithelial apoptosis. Oxford University Press 2009-12 2009-10-13 /pmc/articles/PMC2794158/ /pubmed/19825980 http://dx.doi.org/10.1093/nar/gkp755 Text en © The Author(s) 2009. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Zhang, Xian
Zou, Tongtong
Rao, Jaladanki N.
Liu, Lan
Xiao, Lan
Wang, Peng-Yuan
Cui, Yu-Hong
Gorospe, Myriam
Wang, Jian-Ying
Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines
title Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines
title_full Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines
title_fullStr Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines
title_full_unstemmed Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines
title_short Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines
title_sort stabilization of xiap mrna through the rna binding protein hur regulated by cellular polyamines
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794158/
https://www.ncbi.nlm.nih.gov/pubmed/19825980
http://dx.doi.org/10.1093/nar/gkp755
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