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Tong-Peng Xu, Yan-Fen Wang, Wei-Liang Xiong, Pei Ma, Wen-Yu Wang, Wen-Ming Chen, Ming-De Huang, Rui Xia, Rong Wang, Er-Bao Zhang, Yan-Wen Liu, Wei De, Yong-Qian Shu
Recent evidence indicates that E2F1 transcription factor have pivotal roles in the regulation of cellular processes, and is found to be dysregulated in a variety of cancers. Long non-coding RNAs (lncRNAs) are also reported to exert important effect on tumorigenesis. E2F1 is aberrantly expressed in gastric cancer (GC), and biology functions of E2F1 in GC are controversial. The biological characteristics of E2F1 and correlation between E2F1 and lncRNAs in GC remain to be found. In this study, integrated analysis revealed that E2F1 expression was significantly increased in GC cases and its expression was positively correlated with the poor pathologic stage, large tumor size and poor prognosis...
June 1, 2017: Cell Death & Disease
Kevin Cheung, Cristian A Droppelmann, Adam MacLellan, Ian Cameron, Benjamin Withers, Danae Campos-Melo, Kathryn Volkening, Michael J Strong
Rho guanine nucleotide exchange factor (RGNEF) is a 190kDa RNA binding protein (RBP) that also contains a Dbl/PH domain capable of RhoA activation. Consistent with a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), RGNEF forms pathological neuronal cytoplasmic inclusions in degenerating spinal motor neurons. To further understand the role of RGNEF in the stress response, we first observed that the expression of RGNEF is upregulated in murine spinal motor neurons following distal sciatic nerve injury...
May 8, 2017: Molecular and Cellular Neurosciences
Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher, Kazuko Nishikura
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats...
June 2017: Nature Structural & Molecular Biology
Tara E Crawford Parks, Aymeric Ravel-Chapuis, Emma Bondy-Chorney, Jean-Marc Renaud, Jocelyn Côté, Bernard J Jasmin
Converging lines of evidence have now highlighted the key role for post-transcriptional regulation in the neuromuscular system. In particular, several RNA-binding proteins are known to be misregulated in neuromuscular disorders including myotonic dystrophy type 1, spinal muscular atrophy and amyotrophic lateral sclerosis. In this study, we focused on the RNA-binding protein Staufen1, which assumes multiple functions in both skeletal muscle and neurons. Given our previous work that showed a marked increase in Staufen1 expression in various physiological and pathological conditions including denervated muscle, in embryonic and undifferentiated skeletal muscle, in rhabdomyosarcomas as well as in myotonic dystrophy type 1 muscle samples from both mouse models and humans, we investigated the impact of sustained Staufen1 expression in postnatal skeletal muscle...
May 15, 2017: Human Molecular Genetics
Tara E Crawford Parks, Kristen A Marcellus, Jonathan Langill, Aymeric Ravel-Chapuis, Jean Michaud, Kyle N Cowan, Jocelyn Côté, Bernard J Jasmin
Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes. Recently, we uncovered a key role for the RNA-binding protein Staufen1 during myogenic differentiation through the regulation of c-myc translation. Given the known implication of c-myc in rhabdomyosarcoma, we hypothesized in the current work that Staufen1 controls rhabdomyosarcoma tumorigenesis...
February 17, 2017: Scientific Reports
Emma Bondy-Chorney, Tara E Crawford Parks, Aymeric Ravel-Chapuis, Bernard J Jasmin, Jocelyn Côté
In a recent issue of PLOS Genetics, we reported that the double-stranded RNA-binding protein, Staufen1, functions as a disease modifier in the neuromuscular disorder Myotonic Dystrophy Type I (DM1). In this work, we demonstrated that Staufen1 regulates the alternative splicing of exon 11 of the human Insulin Receptor, a highly studied missplicing event in DM1, through Alu elements located in an intronic region. Furthermore, we found that Staufen1 overexpression regulates numerous alternative splicing events, potentially resulting in both positive and negative effects in DM1...
2016: Rare Diseases
Florence Bonnet-Magnaval, Céline Philippe, Loïc Van Den Berghe, Hervé Prats, Christian Touriol, Eric Lacazette
Under physiological stress conditions the cell protects itself through a global blockade on cap-dependent translation of mRNA. This allows cap-independent mechanisms such as internal ribosome entry site (IRES)-mediated translation to take over and initiate the translation of a specific pool of mRNAs that encode proteins involved in protecting the cell from stress. Staufen 1 (Stau1) is an RNA-binding protein that has been previously implicated in the regulation of stress granule formation and therefore could play a key role in protecting the cell against stress stimuli such as oxidative and endoplasmic reticulum (ER) stress...
October 14, 2016: Biochemical and Biophysical Research Communications
Updesh Dixit, Ashutosh K Pandey, Priya Mishra, Amitabha Sengupta, Virendra N Pandey
Persistent hepatitis C virus (HCV) infection leads to chronic hepatitis C (CHC), which often progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The molecular mechanisms that establish CHC and cause its subsequent development into LC and HCC are poorly understood. We have identified a cytoplasmic double-stranded RNA binding protein, Stau1, which is crucial for HCV replication. In this study, Stau1 specifically interacted with the variable-stem-loop region in the 3' NTR and domain IIId of the HCV-IRES in the 5' NTR, and promoted HCV replication and translation...
June 20, 2016: Nucleic Acids Research
Aymeric Ravel-Chapuis, Amanda Klein Gunnewiek, Guy Bélanger, Tara E Crawford Parks, Jocelyn Côté, Bernard J Jasmin
Myotonic dystrophy (DM1) is caused by an expansion of CUG repeats (CUG(exp)) in the DMPK mRNA 3'UTR. CUG(exp)-containing mRNAs become toxic to cells by misregulating RNA-binding proteins. Here we investigated the consequence of this RNA toxicity on the cellular stress response. We report that cell stress efficiently triggers formation of stress granules (SGs) in proliferating, quiescent, and differentiated muscle cells, as shown by the appearance of distinct cytoplasmic TIA-1- and DDX3-containing foci. We show that Staufen1 is also dynamically recruited into these granules...
June 1, 2016: Molecular Biology of the Cell
Emma Bondy-Chorney, Tara E Crawford Parks, Aymeric Ravel-Chapuis, Roscoe Klinck, Lynda Rocheleau, Martin Pelchat, Benoit Chabot, Bernard J Jasmin, Jocelyn Côté
Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by an expansion of CUG repeats in the 3' UTR of the DMPK gene. The CUG repeats form aggregates of mutant mRNA, which cause misregulation and/or sequestration of RNA-binding proteins, causing aberrant alternative splicing in cells. Previously, we showed that the multi-functional RNA-binding protein Staufen1 (Stau1) was increased in skeletal muscle of DM1 mouse models and patients. We also showed that Stau1 rescues the alternative splicing profile of pre-mRNAs, e...
January 2016: PLoS Genetics
Noga Gershoni-Emek, Arnon Mazza, Michael Chein, Tal Gradus-Pery, Xin Xiang, Ka Wan Li, Roded Sharan, Eran Perlson
Synapse disruption takes place in many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the mechanistic understanding of this process is still limited. We set out to study a possible role for dynein in synapse integrity. Cytoplasmic dynein is a multisubunit intracellular molecule responsible for diverse cellular functions, including long-distance transport of vesicles, organelles, and signaling factors toward the cell center. A less well-characterized role dynein may play is the spatial clustering and anchoring of various factors including mRNAs in distinct cellular domains such as the neuronal synapse...
February 2016: Molecular & Cellular Proteomics: MCP
Sandra M Fernández Moya, Michael A Kiebler
hiCLIP (RNA hybrid and individual-nucleotide resolution ultraviolet cross-linking and immunoprecipitation), is a novel technique developed by Sugimoto et al. (2015). Here, the use of different adaptors permits a controlled ligation of the two strands of a RNA duplex allowing the identification of each arm in the duplex upon sequencing. The authors chose a notoriously difficult to study double-stranded RNA-binding protein (dsRBP) termed Staufen1, a mammalian homolog of Drosophila Staufen involved in mRNA localization and translational control...
October 2015: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Xinlei Wang, Lela Vukovic, Hye Ran Koh, Klaus Schulten, Sua Myong
Double-stranded (ds) RNA is a key player in numerous biological activities in cells, including RNA interference, anti-viral immunity and mRNA transport. The class of proteins responsible for recognizing dsRNA is termed double-stranded RNA binding proteins (dsRBP). However, little is known about the molecular mechanisms underlying the interaction between dsRBPs and dsRNA. Here we examined four human dsRBPs, ADAD2, TRBP, Staufen 1 and ADAR1 on six dsRNA substrates that vary in length and secondary structure. We combined single molecule pull-down (SiMPull), single molecule protein-induced fluorescence enhancement (smPIFE) and molecular dynamics (MD) simulations to investigate the dsRNA-dsRBP interactions...
September 3, 2015: Nucleic Acids Research
T-P Xu, X-X Liu, R Xia, L Yin, R Kong, W-M Chen, M-D Huang, Y-Q Shu
The long noncoding RNA TINCR shows aberrant expression in human squamous carcinomas. However, its expression and function in gastric cancer remain unclear. We report that TINCR is strongly upregulated in human gastric carcinoma (GC), where it was found to contribute to oncogenesis and cancer progression. We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines...
November 5, 2015: Oncogene
Joan Peredo, Patricia Villacé, Juan Ortín, Susana de Lucas
Double-stranded RNA-binding proteins are key elements in the intracellular localization of mRNA and its local translation. Staufen is a double-stranded RNA binding protein involved in the localised translation of specific mRNAs during Drosophila early development and neuronal cell fate. The human homologue Staufen1 forms RNA-containing complexes that include proteins involved in translation and motor proteins to allow their movement within the cell, but the mechanism underlying translation repression in these complexes is poorly understood...
2014: PloS One
Aymeric Ravel-Chapuis, Tara E Crawford, Marie-Laure Blais-Crépeau, Guy Bélanger, Chase T Richer, Bernard J Jasmin
Recent work has shown that Staufen1 plays key roles in skeletal muscle, yet little is known about its pattern of expression during embryonic and postnatal development. Here we first show that Staufen1 levels are abundant in mouse embryonic muscles and that its expression decreases thereafter, reaching low levels in mature muscles. A similar pattern of expression is seen as cultured myoblasts differentiate into myotubes. Muscle degeneration/regeneration experiments revealed that Staufen1 increases after cardiotoxin injection before returning to the low levels seen in mature muscles...
November 15, 2014: Molecular Biology of the Cell
Karine Boulay, Mehdi Ghram, Wildriss Viranaicken, Véronique Trépanier, Stéphanie Mollet, Céline Fréchina, Luc DesGroseillers
Staufen1 (Stau1) is a ribonucleic acid (RNA)-binding protein involved in the post-transcriptional regulation of gene expression. Recent studies indicate that Stau1-bound messenger RNAs (mRNAs) mainly code for proteins involved in transcription and cell cycle control. Consistently, we report here that Stau1 abundance fluctuates through the cell cycle in HCT116 and U2OS cells: it is high from the S phase to the onset of mitosis and rapidly decreases as cells transit through mitosis. Stau1 down-regulation is mediated by the ubiquitin-proteasome system and the E3 ubiquitin ligase anaphase promoting complex/cyclosome (APC/C)...
July 2014: Nucleic Acids Research
Min Young Kim, Jungyun Park, Jong Joo Lee, Dae Hyun Ha, Jonghwan Kim, Chan Gil Kim, Jungwook Hwang, Chul Geun Kim
Requiem (REQ/DPF2) was originally identified as an apoptosis-inducing protein in mouse myeloid cells and belongs to the novel Krüppel-type zinc finger d4-protein family of proteins, which includes neuro-d4 (DPF1) and cer-d4 (DPF3). Interestingly, when a portion of the REQ messenger ribonucleic acid (mRNA) 3' untranslated region (3'UTR), referred to as G8, was overexpressed in K562 cells, β-globin expression was induced, suggesting that the 3'UTR of REQ mRNA plays a physiological role. Here, we present evidence that the REQ mRNA 3'UTR, along with its trans-acting factor, Staufen1 (STAU1), is able to reduce the level of REQ mRNA via STAU1-mediated mRNA decay (SMD)...
June 2014: Nucleic Acids Research
Guo-zheng Li, Jing-jing Guo, Cong-bin Peng
OBJECTIVE: To search for an appropriate animal model that is more closely related to human to study cAMP-response element binding protein target gene Staufen and to identify its location. METHODS: The phylogenetic tree was constructed with Staufen protein (STAUFEN) sequences of different species, and the most suitable animal model was selected by analyzing relativity among them. The Staufen fragments were amplified with reverse transcription-PCR and inserted into a vector and then the sub-clone was transformed into bacteria, selected, amplified, extracted and sequenced...
January 2014: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Susana de Lucas, Juan Carlos Oliveros, Mónica Chagoyen, Juan Ortín
Cellular messenger RNAs (mRNAs) are associated to proteins in the form of ribonucleoprotein particles. The double-stranded RNA-binding (DRB) proteins play important roles in mRNA synthesis, modification, activity and decay. Staufen is a DRB protein involved in the localized translation of specific mRNAs during Drosophila early development. The human Staufen1 (hStau1) forms RNA granules that contain translation regulation proteins as well as cytoskeleton and motor proteins to allow the movement of the granule on microtubules, but the mechanisms of hStau1-RNA recognition are still unclear...
April 2014: Nucleic Acids Research
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