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

2016 ◽  
Vol 473 (11) ◽  
pp. 1641-1649 ◽  
Author(s):  
Yanwu Li ◽  
Gang Chen ◽  
Jun-Yao Wang ◽  
Tongtong Zou ◽  
Lan Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rna Binding ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Low Density Lipoprotein ◽  
Rna Binding Protein ◽  
Density Lipoprotein ◽  
Transcriptional Level ◽  
Intestinal Epithelial ◽  
Repressive Effect

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.

scholarly journals Transcriptional regulation of importin-α1 by JunD modulates subcellular localization of RNA-binding protein HuR in intestinal epithelial cells

2016 ◽  
Vol 311 (6) ◽  
pp. C874-C883 ◽  
Author(s):  
Yan Xu ◽  
Jie Chen ◽  
Lan Xiao ◽  
Hee Kyoung Chung ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Subcellular Localization ◽  
Rna Binding ◽  
Nuclear Translocation ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Intestinal Epithelial ◽  
Mucosal Regeneration ◽  
Importin Α

The RNA-binding protein HuR is crucial for normal intestinal mucosal regeneration by modulating the stability and translation of target mRNAs, but the exact mechanism underlying HuR trafficking between the cytoplasm and nucleus remains largely unknown. Here we report a novel function of transcription factor JunD in the regulation of HuR subcellular localization through the control of importin-α1 expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically inhibited importin-α1 at the transcription level, and this repression is mediated via interaction with CREB-binding site that was located at the proximal region of importin-α1 promoter. Reduction in the levels of importin-α1 by JunD increased cytoplasmic levels of HuR, although it failed to alter whole cell HuR levels. Increased levels of endogenous JunD by depleting cellular polyamines also inhibited importin-α1 expression and increased cytoplasmic HuR levels, whereas JunD silencing rescued importin-α1 expression and enhanced HuR nuclear translocation in polyamine-deficient cells. Moreover, importin-α1 silencing protected IECs against apoptosis, which was prevented by HuR silencing. These results indicate that JunD regulates HuR subcellular distribution by downregulating importin-α1, thus contributing to the maintenance of gut epithelium homeostasis.

scholarly journals Novel intestinal splice variants of RNA-binding protein CUGBP2: isoform-specific effects on mitotic catastrophe

2008 ◽  
Vol 294 (4) ◽  
pp. G971-G981 ◽  
Author(s):  
Satish Ramalingam ◽  
Gopalan Natarajan ◽  
Chris Schafer ◽  
Dharmalingam Subramaniam ◽  
Randal May ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rna Binding ◽  
Intestinal Epithelial Cells ◽  
Splice Variants ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cyclin B1 ◽  
Mitotic Catastrophe ◽  
Intestinal Epithelial ◽  
Cox 2

CUG triplet repeat-binding protein 2 (CUGBP2) is a RNA-binding protein that regulates mRNA translation and modulates apoptosis. Here, we report the identification of two splice variants (termed variants 2 and 3) in cultured human intestinal epithelial cells and in mouse gastrointestinal tract. The variants are generated from alternative upstream promoters resulting in the inclusion of additional NH2-terminal residues. Although variant 2 is the predominant isoform in normal intestine, its expression is reduced, whereas variant 1 is overexpressed following γ-irradiation. All three variants bind cyclooxygenase-2 (COX-2) mRNA. However, only variant 1 inhibits the translation of the endogenous COX-2 mRNA and a chimeric luciferase mRNA containing the COX-2 3′untranslated region. Furthermore, whereas variant 1 is predominantly nuclear, variants 2 and 3 are predominantly cytoplasmic. These data imply that the additional amino acids affect CUGBP2 function. Previous studies have demonstrated that variant 1 induces intestinal epithelial cells to undergo apoptosis. However, in contrast to variant 1, the two novel variants do not affect proliferation or apoptosis of HCT116 cells. In addition, only variant 1 induced G2/M cell cycle arrest, which was overcome by prostaglandin E2. Moreover, variant 1 increased cellular levels of phosphorylated p53 and Bax and decreased Bcl2. Caspase-3 and -9 were also activated, suggesting the initiation of the intrinsic apoptotic pathway. Furthermore, increased phosphorylation of checkpoint kinase (Chk)1 and Chk2 kinases and increased nuclear localization of Cdc2 and cyclin B1 suggested that cells were in mitotic transition. Taken together, these data demonstrate that cells expressing CUGBP2 variant 1 undergo apoptosis during mitosis, suggesting mitotic catastrophe.

Polarised distribution of the RNA-binding protein Staufen in differentiated intestinal epithelial cells

FEBS Letters ◽  
2005 ◽  
Vol 579 (10) ◽  
pp. 2226-2230 ◽  
Author(s):  
Hannah Gautrey ◽  
Josie McConnell ◽  
Judith Hall ◽  
John Hesketh
Keyword(s):  
Epithelial Cells ◽  
Rna Binding ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Intestinal Epithelial

M1862 Activation of Wnt Signaling Protects Intestinal Epithelial Cells from Apoptosis By Increasing Cytoplasmic Levels of RNA-Binding Protein HuR

2008 ◽  
Vol 134 (4) ◽  
pp. A-877
Author(s):  
Emily C. Bellavance ◽  
Lan Liu ◽  
Rao N. Jaladanki ◽  
Tongtong Zou ◽  
Douglas J. Turner ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Wnt Signaling ◽  
Rna Binding ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Intestinal Epithelial

131 RNA-Binding Protein HuR Regulates MicroRNA Processing by Altering Drosha Expression in Intestinal Epithelial Cells

2013 ◽  
Vol 144 (5) ◽  
pp. S-31
Author(s):  
Ran Zhuang ◽  
Rao N Jaladanki ◽  
Tongtong Zou ◽  
Lan Xiao ◽  
Natasha Z Hansraj ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rna Binding ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Intestinal Epithelial ◽  
Microrna Processing

scholarly journals Tissue-specific sorting of the human LDL receptor in polarized epithelia of transgenic mice.

1990 ◽  
Vol 111 (2) ◽  
pp. 347-359 ◽  
Author(s):  
R K Pathak ◽  
M Yokode ◽  
R E Hammer ◽  
S L Hofmann ◽  
M S Brown ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transgenic Mice ◽  
Intestinal Epithelial Cells ◽  
Low Density Lipoprotein ◽  
Human Fibroblasts ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Intestinal Epithelial ◽  
Coated Pits ◽  
Ldl Receptors

The distribution of human low density lipoprotein (LDL) receptors was studied by immunofluorescence and immunoelectron microscopy in epithelial cells of transgenic mice that express high levels of receptors under control of the metallothionein-I promoter. In hepatocytes and intestinal epithelial cells, the receptors were confined to the basal and basolateral surfaces, respectively. Very few LDL receptors were present in coated pits or intracellular vesicles. In striking contrast, in the epithelium of the renal tubule the receptors were present on the apical (lumenal) surface where they appeared to be concentrated at the base of microvilli and were abundant in vesicles of the endocytic recycling pathway. Intravenously administered LDL colloidal gold conjugates bound to the receptors on hepatocyte microvilli and were slowly internalized, apparently through slow migration into coated pits. We conclude that (a) sorting of LDL receptors to the surface of different epithelial cells varies with each tissue; and (b) in addition to a signal for clustering in coated pits, the LDL receptor may contain a signal for retention in noncoated membrane that is manifest in hepatocytes and intestinal epithelial cells, but not in renal epithelial cells or cultured human fibroblasts.

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