scholarly journals Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip

2017 ◽  
Vol 199 (11) ◽  
pp. 3892-3899 ◽  
Author(s):  
Smita Kulkarni ◽  
Veron Ramsuran ◽  
Marijana Rucevic ◽  
Sukhvinder Singh ◽  
Alexandra Lied ◽  
...  
Keyword(s):  
Protein Expression ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Alternative Polyadenylation ◽  
Polyadenylation Signals

scholarly journals RNA-binding protein DDX3 mediates posttranscriptional regulation of androgen receptor: A mechanism of castration resistance

2020 ◽  
Vol 117 (45) ◽  
pp. 28092-28101 ◽  
Author(s):  
Jordan E. Vellky ◽  
Sean T. McSweeney ◽  
Emily A. Ricke ◽  
William A. Ricke
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Messenger Rna ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Translation

Prostate cancer (CaP) driven by androgen receptor (AR) is treated with androgen deprivation; however, therapy failure results in lethal castration-resistant prostate cancer (CRPC). AR-low/negative (ARL/−) CRPC subtypes have recently been characterized and cannot be targeted by hormonal therapies, resulting in poor prognosis. RNA-binding protein (RBP)/helicase DDX3 (DEAD-box helicase 3 X-linked) is a key component of stress granules (SG) and is postulated to affect protein translation. Here, we investigated DDX3-mediated posttranscriptional regulation of AR mRNA (messenger RNA) in CRPC. Using patient samples and preclinical models, we objectively quantified DDX3 and AR expression in ARL/− CRPC. We utilized CRPC models to identify DDX3:AR mRNA complexes by RNA immunoprecipitation, assess the effects of DDX3 gain/loss-of-function on AR expression and signaling, and address clinical implications of targeting DDX3 by assessing sensitivity to AR-signaling inhibitors (ARSI) in CRPC xenografts in vivo. ARL/− CRPC expressed abundant AR mRNA despite diminished levels of AR protein. DDX3 protein was highly expressed in ARL/− CRPC, where it bound to AR mRNA. Consistent with a repressive regulatory role, DDX3 localized to cytoplasmic puncta with SG marker PABP1 in CRPC. While induction of DDX3-nucleated SGs resulted in decreased AR protein expression, inhibiting DDX3 was sufficient to restore 1) AR protein expression, 2) AR signaling, and 3) sensitivity to ARSI in vitro and in vivo. Our findings implicate the RBP protein DDX3 as a mechanism of posttranscriptional regulation for AR in CRPC. Clinically, DDX3 may be targetable for sensitizing ARL/− CRPC to AR-directed therapies.

scholarly journals The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages

2011 ◽  
Vol 22 (16) ◽  
pp. 2875-2885 ◽  
Author(s):  
Mai Nguyen Chi ◽  
Jacques Auriol ◽  
Bernard Jégou ◽  
Dimitris L. Kontoyiannis ◽  
James M.A. Turner ◽  
...  
Keyword(s):  
Germ Cells ◽  
Posttranscriptional Regulation ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Female Sterility ◽  
Targeted Deletion

Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR.

scholarly journals Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP 1/ IGF 2 BP 1

EMBO Reports ◽  
2019 ◽  
Vol 20 (6) ◽  
Author(s):  
Priya Chatterji ◽  
Patrick A Williams ◽  
Kelly A Whelan ◽  
Fernando C Samper ◽  
Sarah F Andres ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Epithelial Repair

Cold-induced RNA-binding protein (CIRBP) regulates the expression of Src-associated during mitosis of 68 kDa (Sam68) and extracellular signal-regulated kinases (ERK) during heat stress-induced testicular injury

2020 ◽  
Vol 32 (18) ◽  
pp. 1357
Author(s):  
Chengcheng Xu ◽  
Dandan Ke ◽  
Liping Zou ◽  
Nianyu Li ◽  
Yingying Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Protein Expression ◽  
Rna Binding ◽  
Cell Model ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Testicular Injury

In this study, the ability of cold-induced RNA-binding protein (CIRBP) to regulate the expression of Src-associated during mitosis of 68 kDa (Sam68) and extracellular signal-regulated kinases (ERK) in the mouse testis and mouse primary spermatocytes (GC-2spd cell line) before and after heat stress was examined to explore the molecular mechanism by which CIRBP decreases testicular injury. A mouse testicular hyperthermia model, a mouse primary spermatocyte hyperthermia model and a low CIRBP gene-expression cell model were constructed and their relevant parameters were analysed. The mRNA and protein levels of CIRBP and Sam68 were significantly decreased in the 3-h and 12-h testicular heat-stress groups, extracellular signal-regulated kinase 1/2 (ERK1/2) protein expression was not significantly affected but phospho-ERK1/2 protein levels were significantly decreased. GC-2spd cellular heat-stress results showed that the mRNA and protein concentrations of CIRBP and Sam68 were reduced 48h after heat stress. In the low CIRBP gene-expression cell model, CIRBP protein expression was significantly decreased. Sam68 mRNA expression was significantly decreased only at the maximum transfection concentration of 50nM and Sam68 protein expression was not significantly affected. These findings suggest that CIRBP may regulate the expression of Sam68 at the transcriptional level and the expression of phospho-ERK1/2 protein, both of which protect against heat-stress-induced testicular injury in mice.

Role of the RNA-binding protein HuR in posttranscriptional regulation of IL-13 in T cells

2007 ◽  
Vol &NA; ◽  
pp. S35
Author(s):  
Cristiana Stellato ◽  
J Fang ◽  
B Tancowny ◽  
J Fan ◽  
F Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruben G. de Bruin ◽  
Eric P. van der Veer ◽  
Jurriën Prins ◽  
Dae Hyun Lee ◽  
Martijn J. C. Dane ◽  
...  
Keyword(s):  
Protein Expression ◽  
Barrier Function ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function

scholarly journals RNA-Binding Protein HuR Is Required for Stabilization of SLC11A1 mRNA and SLC11A1 Protein Expression

2005 ◽  
Vol 25 (18) ◽  
pp. 8139-8149 ◽  
Author(s):  
Yong Zhong Xu ◽  
Sergio Di Marco ◽  
Imed Gallouzi ◽  
Marek Rola-Pleszczynski ◽  
Danuta Radzioch
Keyword(s):  
Posttranscriptional Regulation ◽  
Macrophage Activation ◽  
Rna Binding ◽  
Binding Protein ◽  
Mrna Level ◽  
Rna Binding Protein ◽  
Cytoplasmic Localization ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Solute Carrier

ABSTRACT The solute carrier family 11 member 1 (SLC11A1, formerly NRAMP1) gene is associated with infectious and autoimmune diseases and plays an important role in macrophage activation. Human SLC11A1 mRNA contains an AU-rich element (ARE) within the 3′ untranslated region; however, its role in the regulation of SLC11A1 gene expression has not been elucidated. Here we analyze the expression of SLC11A1 in human monocytes and HL-60 cells and then use HL-60 cells as a model to determine whether RNA-binding protein HuR is associated with the ARE and involved in SLC11A1 mRNA turnover. Our results demonstrate a binding of HuR to the SLC11A1 ARE in phorbol myristate acetate (PMA)-differentiated cells dramatically increased compared to that in undifferentiated cells. Interestingly, PMA-induced accumulation of cytoplasmic HuR occurs in parallel with an increase in the binding of HuR to SLC11A1 ARE and with an increase in the SLC11A1 mRNA level. This suggests that HuR's cytoplasmic localization plays an important role in the regulation of SLC11A1 expression. We also observe that down-regulation of HuR expression by RNA interference (RNAi) results in a decrease in SLC11A1 expression which can be restored by the addition of recombinant HuR protein to the RNAi-treated cells. Finally, we show that HuR overexpression in HL-60 cells significantly increases the SLC11A1 mRNA stability. Taken together, our data demonstrate that HuR is a key mediator of posttranscriptional regulation and expression of the SLC11A1 gene.

scholarly journals RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism

2017 ◽  
Vol 127 (10) ◽  
pp. 3741-3754 ◽  
Author(s):  
Elizabeth J. Tarling ◽  
Bethan L. Clifford ◽  
Joan Cheng ◽  
Pauline Morand ◽  
Angela Cheng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Posttranscriptional Regulation ◽  
Acid Metabolism ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Bile Acid Metabolism

scholarly journals Caspase-mediated Cleavage of RNA-binding Protein HuR Regulates c-Myc Protein Expression after Hypoxic Stress

2011 ◽  
Vol 286 (37) ◽  
pp. 32333-32343 ◽  
Author(s):  
Sudha Talwar ◽  
Junfei Jin ◽  
Brittany Carroll ◽  
Angen Liu ◽  
Marion Boyd Gillespie ◽  
...  
Keyword(s):  
Protein Expression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Hypoxic Stress
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