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Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells

MicroRNAs (miRNAs) control gene expression by binding to their target mRNAs for degradation and/or translation repression and are implicated in many aspects of cellular physiology. Our previous study shows that miR-29b acts as a biological repressor of intestinal mucosal growth, but its exact downst...

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Autores principales: Li, Yanwu, Chen, Gang, Wang, Jun-Yao, Zou, Tongtong, Liu, Lan, Xiao, Lan, Chung, Hee Kyoung, Rao, Jaladanki N., Wang, Jian-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888462/
https://www.ncbi.nlm.nih.gov/pubmed/27089893
http://dx.doi.org/10.1042/BCJ20160057
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author Li, Yanwu
Chen, Gang
Wang, Jun-Yao
Zou, Tongtong
Liu, Lan
Xiao, Lan
Chung, Hee Kyoung
Rao, Jaladanki N.
Wang, Jian-Ying
author_facet Li, Yanwu
Chen, Gang
Wang, Jun-Yao
Zou, Tongtong
Liu, Lan
Xiao, Lan
Chung, Hee Kyoung
Rao, Jaladanki N.
Wang, Jian-Ying
author_sort Li, Yanwu
collection PubMed
description MicroRNAs (miRNAs) control gene expression by binding to their target mRNAs for degradation and/or translation repression and are implicated in many aspects of cellular physiology. Our previous study shows that miR-29b acts as a biological repressor of intestinal mucosal growth, but its exact downstream targets remain largely unknown. In the present study, we found that mRNAs, encoding Wnt co-receptor LRP6 (low-density lipoprotein-receptor-related protein 6) and RNA-binding protein (RBP) HuR, are novel targets of miR-29b in intestinal epithelial cells (IECs) and that expression of LRP6 and HuR is tightly regulated by miR-29b at the post-transcriptional level. miR-29b interacted with both Lrp6 and HuR mRNAs via their 3′-UTRs and inhibited LRP6 and HuR expression by destabilizing Lrp6 and HuR mRNAs and repressing their translation. Studies using heterologous reporter constructs revealed a greater repressive effect of miR-29b through a single binding site in the Lrp6 or HuR 3′-UTR, whereas deletion mutation of this site prevented miR-29b-induced repression of LRP6 and HuR expression. Repression of HuR by miR-29b in turn also contributed to miR-29b-induced LRP6 inhibition, since ectopic overexpression of HuR in cells overexpressing miR-29b restored LRP6 expression to near normal levels. Taken together, our results suggest that miR-29b inhibits expression of LRP6 and HuR post-transcriptionally, thus playing a role in the regulation of IEC proliferation and intestinal epithelial homoeostasis.
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spelling pubmed-48884622016-06-08 Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells Li, Yanwu Chen, Gang Wang, Jun-Yao Zou, Tongtong Liu, Lan Xiao, Lan Chung, Hee Kyoung Rao, Jaladanki N. Wang, Jian-Ying Biochem J Research Articles MicroRNAs (miRNAs) control gene expression by binding to their target mRNAs for degradation and/or translation repression and are implicated in many aspects of cellular physiology. Our previous study shows that miR-29b acts as a biological repressor of intestinal mucosal growth, but its exact downstream targets remain largely unknown. In the present study, we found that mRNAs, encoding Wnt co-receptor LRP6 (low-density lipoprotein-receptor-related protein 6) and RNA-binding protein (RBP) HuR, are novel targets of miR-29b in intestinal epithelial cells (IECs) and that expression of LRP6 and HuR is tightly regulated by miR-29b at the post-transcriptional level. miR-29b interacted with both Lrp6 and HuR mRNAs via their 3′-UTRs and inhibited LRP6 and HuR expression by destabilizing Lrp6 and HuR mRNAs and repressing their translation. Studies using heterologous reporter constructs revealed a greater repressive effect of miR-29b through a single binding site in the Lrp6 or HuR 3′-UTR, whereas deletion mutation of this site prevented miR-29b-induced repression of LRP6 and HuR expression. Repression of HuR by miR-29b in turn also contributed to miR-29b-induced LRP6 inhibition, since ectopic overexpression of HuR in cells overexpressing miR-29b restored LRP6 expression to near normal levels. Taken together, our results suggest that miR-29b inhibits expression of LRP6 and HuR post-transcriptionally, thus playing a role in the regulation of IEC proliferation and intestinal epithelial homoeostasis. Portland Press Ltd. 2016-05-27 2016-06-01 /pmc/articles/PMC4888462/ /pubmed/27089893 http://dx.doi.org/10.1042/BCJ20160057 Text en © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
spellingShingle Research Articles
Li, Yanwu
Chen, Gang
Wang, Jun-Yao
Zou, Tongtong
Liu, Lan
Xiao, Lan
Chung, Hee Kyoung
Rao, Jaladanki N.
Wang, Jian-Ying
Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells
title Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells
title_full Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells
title_fullStr Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells
title_full_unstemmed Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells
title_short Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells
title_sort post-transcriptional regulation of wnt co-receptor lrp6 and rna-binding protein hur by mir-29b in intestinal epithelial cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888462/
https://www.ncbi.nlm.nih.gov/pubmed/27089893
http://dx.doi.org/10.1042/BCJ20160057
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