miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis

When neuroblasts divide, prospero protein and mRNA segregate asymmetrically into the daughter neuroblast and sibling ganglion mother cell. miranda is known to localize prospero protein to the basal cell cortex of neuroblasts while the staufen RNA-binding protein mediates prospero mRNA localization. Here we show that miranda is required for asymmetric staufen localization in neuroblasts. Analyses using miranda mutants reveal that prospero and staufen interact with miranda under the same cell-cycle-dependent control. miranda thus acts to partition both prospero protein and mRNA. Furthermore, miranda localizes prospero and staufen to the basolateral cortex in dividing epithelial cells, which express the three proteins prior to neurogenesis. Our observations suggest that the epithelial cell and neuroblast (both of epithelial origin) share the same molecular machinery for creating cellular asymmetry.

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

AJP Cell Physiology ◽

10.1152/ajpcell.00209.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. C874-C883 ◽

Cited By ~ 2

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.

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Egalitarian is a selective RNA-binding protein linking mRNA localization signals to the dynein motor

Genes & Development ◽

10.1101/gad.531009 ◽

2009 ◽

Vol 23 (13) ◽

pp. 1546-1558 ◽

Cited By ~ 124

Author(s):

M. Dienstbier ◽

F. Boehl ◽

X. Li ◽

S. L. Bullock

Keyword(s):

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Mrna Localization ◽

Dynein Motor

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Downregulation of the RNA Binding Protein HuR Correlates with Enhanced Expression of Senescence Markers in COPD Bronchial Epithelial Cells

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3771 ◽

2019 ◽

Author(s):

A.E. Wyman ◽

A.J. Dabo ◽

W. Ezegbunam ◽

I. Garcia-Arcos ◽

N. Baumlin-Schmid ◽

...

Keyword(s):

Epithelial Cells ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Enhanced Expression

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A staufen-like RNA-binding protein in translocation channels linking nurse cells to oocytes in Notonecta shows nucleotide-dependent attachment to microtubules

Journal of Cell Science ◽

10.1242/jcs.112.17.2947 ◽

1999 ◽

Vol 112 (17) ◽

pp. 2947-2955

Author(s):

S. Hurst ◽

N.J. Talbot ◽

H. Stebbings

Keyword(s):

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Mrna Localization ◽

Dependent Manner ◽

Nurse Cells ◽

Double Stranded Rna ◽

Standard Procedures ◽

Rna Probes ◽

Peptide Antibody

In Drosophila melanogaster the staufen gene encodes an RNA-binding protein that is essential for the correct localization of certain nurse cell-derived transcripts in oocytes. Although the mechanism underlying mRNA localization is unknown, mRNA-staufen complexes have been shown to move in a microtubule-dependent manner, and it has been suggested that staufen associates with a motor protein which generates the movement. We have investigated this possibility using Notonecta glauca in which nurse cells also supply the oocytes with mRNA, but via greatly extended nutritive tubes comprised of large aggregates of parallel microtubules. Using a staufen peptide antibody and RNA probes we have identified a staufen-like protein, which specifically binds double-stranded RNA, in the nutritive tubes of Notonecta. We show that while the staufen-like protein does not co-purify with microtubules from ovaries using standard procedures it does so under conditions of motor-entrapment, specifically in the presence of AMP-PNP. We also show that the staufen-like protein is subsequently removed by ATP and GTP, but not ADP. Nucleotide-dependent binding to microtubules is typical of a motor-mediated interaction and the pattern of attachment and detachment of the staufen-like protein correlates with that of a kinesin protein within the ovaries. Our findings indicate that the staufen-like RNA-binding protein attaches to, and is transported along, Notonecta ovarian microtubules by a kinesin motor.

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A highly conserved RNA-binding protein for cytoplasmic mRNA localization in vertebrates

Current Biology ◽

10.1016/s0960-9822(98)70200-3 ◽

1998 ◽

Vol 8 (9) ◽

pp. 489-496 ◽

Cited By ~ 154

Author(s):

James O. Deshler ◽

Martin I. Highett ◽

Tatiana Abramson ◽

Bruce J. Schnapp

Keyword(s):

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Mrna Localization

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Interleukin-4-induced posttranscriptional gene regulation of CCL26 by the RNA-binding protein HuR in primary human nasal polyp-derived epithelial cells

International Forum of Allergy & Rhinology ◽

10.1002/alr.22250 ◽

2018 ◽

Vol 9 (3) ◽

pp. 311-321 ◽

Cited By ~ 2

Author(s):

Peng Tian ◽

Huashuang Ou ◽

Fan Wu ◽

Yun Ma ◽

Xiang Liu ◽

...

Keyword(s):

Gene Regulation ◽

Epithelial Cells ◽

Nasal Polyp ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Interleukin 4 ◽

Posttranscriptional Gene Regulation

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The RNA-binding protein HuR stabilizes survivin mRNA in human oesophageal epithelial cells

Biochemical Journal ◽

10.1042/bj20110028 ◽

2011 ◽

Vol 437 (1) ◽

pp. 89-96 ◽

Cited By ~ 23

Author(s):

James M. Donahue ◽

Elizabeth T. Chang ◽

Lan Xiao ◽

Peng-Yuan Wang ◽

Jaladanki N. Rao ◽

...

Keyword(s):

Epithelial Cells ◽

Oesophageal Cancer ◽

Mrna Stability ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Survivin Expression ◽

Transcriptional Level ◽

Survivin Mrna ◽

Hu Antigen R

Overexpression of survivin, a member of the IAP (inhibitor of apoptosis) family, has been correlated with poorer outcomes in multiple malignancies, including oesophageal cancer. The regulatory mechanisms, particularly at the post-transcriptional level, involved in survivin overexpression are not well understood. Previous work from our group has shown that the RNA-binding protein HuR (Hu antigen R), which is also overexpressed in several malignancies, stabilizes the mRNA of XIAP (X-linked IAP), another IAP family member. In the present study, we demonstrate the binding of HuR to a 288 bp fragment in the 3′-UTR (untranslated region) of survivin mRNA in human oesophageal epithelial cells. Unexpectedly, overexpression of HuR led to a decrease in survivin expression. This was associated with decreased survivin mRNA and promoter activity, suggesting a decrease in transcription. Levels of p53, a negative transcriptional regulator of survivin, increased following HuR overexpression, in conjunction with enhanced p53 mRNA stability. Silencing p53 prior to HuR overexpression resulted in increased survivin protein and mRNA stability. These results demonstrate that, in the absence of p53, HuR overexpression results in increased survivin mRNA stability and protein expression. This provides an additional explanation for the increased survivin expression observed in oesophageal cancer cells that have lost p53.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00540.2007 ◽

2008 ◽

Vol 294 (4) ◽

pp. G971-G981 ◽

Cited By ~ 22

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.

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