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Bastian Popper, Antonia Demleitner, Valerie J Bolivar, Gretchen Kusek, Abigail Snyder-Keller, Rico Schieweck, Sally Temple, Michael A Kiebler
Staufen2 (Stau2) is a double-stranded RNA-binding protein (RBP) involved in posttranscriptional gene expression control in neurons. In flies, staufen contributes to learning and long-term memory formation. To study the impact of mammalian Stau2 on behavior, we generated a novel gene-trap mouse model that yields significant constitutive downregulation of Stau2 (Stau2GT ). In order to investigate the effect of Stau2 downregulation on hippocampus-dependent behavior, we performed a battery of behavioral assays, i...
April 2018: Neurobiology of Learning and Memory
Stefan M Berger, Iván Fernández-Lamo, Kai Schönig, Sandra M Fernández Moya, Janina Ehses, Rico Schieweck, Stefano Clementi, Thomas Enkel, Sascha Grothe, Oliver von Bohlen Und Halbach, Inmaculada Segura, José María Delgado-García, Agnès Gruart, Michael A Kiebler, Dusan Bartsch
BACKGROUND: Dendritic messenger RNA (mRNA) localization and subsequent local translation in dendrites critically contributes to synaptic plasticity and learning and memory. Little is known, however, about the contribution of RNA-binding proteins (RBPs) to these processes in vivo. RESULTS: To delineate the role of the double-stranded RBP Staufen2 (Stau2), we generate a transgenic rat model, in which Stau2 expression is conditionally silenced by Cre-inducible expression of a microRNA (miRNA) targeting Stau2 mRNA in adult forebrain neurons...
November 17, 2017: Genome Biology
Tejaswini Sharangdhar, Yoichiro Sugimoto, Jacqueline Heraud-Farlow, Sandra M Fernández-Moya, Janina Ehses, Igor Ruiz de Los Mozos, Jernej Ule, Michael A Kiebler
Dendritic localization and hence local mRNA translation contributes to synaptic plasticity in neurons. Staufen2 (Stau2) is a well-known neuronal double-stranded RNA-binding protein (dsRBP) that has been implicated in dendritic mRNA localization. The specificity of Stau2 binding to its target mRNAs remains elusive. Using individual-nucleotide resolution CLIP (iCLIP), we identified significantly enriched Stau2 binding to the 3'-UTRs of 356 transcripts. In 28 (7.9%) of those, binding occurred to a retained intron in their 3'-UTR The strongest bound 3'-UTR intron was present in the longest isoform of Calmodulin 3 (Calm3L ) mRNA Calm3L 3'-UTR contains six Stau2 crosslink clusters, four of which are in this retained 3'-UTR intron...
October 2017: EMBO Reports
Rémy Beaujois, Elizabeth Ottoni, Xin Zhang, Christina Gagnon, Sami HSine, Stéphanie Mollet, Wildriss Viranaicken, Luc DesGroseillers
BACKGROUND: Staufen2 (STAU2) is an RNA-binding protein involved in the post-transcriptional regulation of gene expression. This protein was shown to be required for organ formation and cell differentiation. Although STAU2 functions have been reported in neuronal cells, its role in dividing cells remains deeply uncharacterized. Especially, its regulation during the cell cycle is completely unknown. RESULTS: In this study, we showed that STAU2 isoforms display a mitosis-specific slow migration pattern on SDS-gels in all tested transformed and untransformed cell lines...
July 14, 2017: BMC Cell Biology
Raúl Ortiz, Maya V Georgieva, Sara Gutiérrez, Neus Pedraza, Sandra M Fernández-Moya, Carme Gallego
Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain...
July 5, 2017: Cell Reports
Ying Li, Yeou-Cherng Bor, Mark P Fitzgerald, Kevin S Lee, David Rekosh, Marie-Louise Hammarskjold
The Nxf1 protein is a major nuclear export receptor for the transport of mRNA, and it also is essential for export of retroviral mRNAs with retained introns. In the latter case, it binds to RNA elements known as constitutive transport elements (CTEs) and functions in conjunction with a cofactor known as Nxt1. The NXF1 gene also regulates expression of its own intron-containing RNA through the use of a functional CTE within intron 10. mRNA containing this intron is exported to the cytoplasm, where it can be translated into the 356-amino acid short Nxf1(sNxf1) protein, despite the fact that it is a prime candidate for nonsense-mediated decay (NMD)...
December 1, 2016: Molecular Biology of the Cell
Yan Cao, Juan Du, Dandan Chen, Qian Wang, Nana Zhang, Xiaoyun Liu, Xiaoyu Liu, Jing Weng, Yuanjing Liang, Wei Ma
Staufen2 (Stau2) is a double-stranded RNA-binding protein involved in cell fate decision by regulating mRNA transport, mRNA stability, translation, and ribonucleoprotein assembly. Little is known about Stau2 expression and function in mammalian oocytes during meiosis. Herein we report the sub-cellular distribution and function of Stau2 in mouse oocyte meiosis. Western blot analysis revealed high and stable expression of Stau2 in oocytes from germinal vesicle (GV) to metaphase II (MII). Immunofluorescence showed that Stau2 was evenly distributed in oocytes at GV stage, and assembled as filaments after germinal vesicle breakdown (GVBD), particularly, colocalized with spindle at MI and MII...
October 2016: Cell Cycle
Xin Zhang, Véronique Trépanier, Remy Beaujois, Wildriss Viranaicken, Elliot Drobetsky, Luc DesGroseillers
Staufen2 (Stau2) is an RNA-binding protein involved in cell fate decision by controlling several facets of mRNA processing including localization, splicing, translation and stability. Herein we report that exposure to DNA-damaging agents that generate replicative stress such as camptothecin (CPT), 5-fluoro-uracil (5FU) and ultraviolet radiation (UVC) causes downregulation of Stau2 in HCT116 colorectal cancer cells. In contrast, other agents such as doxorubicin and ionizing radiation had no effect on Stau2 expression...
May 5, 2016: Nucleic Acids Research
Jacki E Heraud-Farlow, Tejaswini Sharangdhar, Xiao Li, Philipp Pfeifer, Stefanie Tauber, Denise Orozco, Alexandra Hörmann, Sabine Thomas, Anetta Bakosova, Ashley R Farlow, Dieter Edbauer, Howard D Lipshitz, Quaid D Morris, Martin Bilban, Michael Doyle, Michael A Kiebler
RNA-binding proteins play crucial roles in directing RNA translation to neuronal synapses. Staufen2 (Stau2) has been implicated in both dendritic RNA localization and synaptic plasticity in mammalian neurons. Here, we report the identification of functionally relevant Stau2 target mRNAs in neurons. The majority of Stau2-copurifying mRNAs expressed in the hippocampus are present in neuronal processes, further implicating Stau2 in dendritic mRNA regulation. Stau2 targets are enriched for secondary structures similar to those identified in the 3' UTRs of Drosophila Staufen targets...
December 26, 2013: Cell Reports
Renate Fritzsche, Daniela Karra, Keiryn L Bennett, Foong Yee Ang, Jacki E Heraud-Farlow, Marco Tolino, Michael Doyle, Karl E Bauer, Sabine Thomas, Melanie Planyavsky, Eric Arn, Anetta Bakosova, Kerstin Jungwirth, Alexandra Hörmann, Zsofia Palfi, Julia Sandholzer, Martina Schwarz, Paolo Macchi, Jacques Colinge, Giulio Superti-Furga, Michael A Kiebler
Transport of RNAs to dendrites occurs in neuronal RNA granules, which allows local synthesis of specific proteins at active synapses on demand, thereby contributing to learning and memory. To gain insight into the machinery controlling dendritic mRNA localization and translation, we established a stringent protocol to biochemically purify RNA granules from rat brain. Here, we identified a specific set of interactors for two RNA-binding proteins that are known components of neuronal RNA granules, Barentsz and Staufen2...
December 26, 2013: Cell Reports
Eonyoung Park, Michael L Gleghorn, Lynne E Maquat
Staufen (STAU)1-mediated mRNA decay (SMD) is a posttranscriptional regulatory mechanism in mammals that degrades mRNAs harboring a STAU1-binding site (SBS) in their 3'-untranslated regions (3' UTRs). We show that SMD involves not only STAU1 but also its paralog STAU2. STAU2, like STAU1, is a double-stranded RNA-binding protein that interacts directly with the ATP-dependent RNA helicase up-frameshift 1 (UPF1) to reduce the half-life of SMD targets that form an SBS by either intramolecular or intermolecular base-pairing...
January 8, 2013: Proceedings of the National Academy of Sciences of the United States of America
Gretchen Kusek, Melissa Campbell, Frank Doyle, Scott A Tenenbaum, Michael Kiebler, Sally Temple
Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here, we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2(+) neuroblast daughter, taking with it a subset of RNAs...
October 5, 2012: Cell Stem Cell
John P Vessey, Gianluca Amadei, Sarah E Burns, Michael A Kiebler, David R Kaplan, Freda D Miller
The cellular mechanisms that regulate self-renewal versus differentiation of mammalian somatic tissue stem cells are still largely unknown. Here, we asked whether an RNA complex regulates this process in mammalian neural stem cells. We show that the RNA-binding protein Staufen2 (Stau2) is apically localized in radial glial precursors of the embryonic cortex, where it forms a complex with other RNA granule proteins including Pumilio2 (Pum2) and DDX1, and the mRNAs for β-actin and mammalian prospero, prox1. Perturbation of this complex by functional knockdown of Stau2, Pum2, or DDX1 causes premature differentiation of radial glial precursors into neurons and mislocalization and misexpression of prox1 mRNA...
October 5, 2012: Cell Stem Cell
Cassandra K Bilogan, Marko E Horb
Defining the regulatory molecular networks involved in patterning the developing anterior endoderm is essential to understand how the pancreas, liver, stomach, and duodenum are discretely specified from each other. In this study, we analyzed the expression and function of the double-stranded RNA-binding protein Staufen2 in Xenopus laevis endoderm. We found that staufen2 was broadly expressed within the developing endoderm beginning at gastrulation becoming localized to the anterior endoderm at later stages...
March 2012: Genesis: the Journal of Genetics and Development
Takashi Miki, Yasunao Kamikawa, Sadamu Kurono, Yuka Kaneko, Jun Katahira, Yoshihiro Yoneda
UNLABELLED: dendritic mRNA transport machines. Although Stau2 is thought to be involved in the dendritic targeting of several mRNAs in neurons, the mechanism whereby Stau2 regulates these mRNAs is unknown. To elucidate the functions of Stau2, we screened for novel binding partners by affinity purification of GST-tagged Stau2 from 293F cells. RESULTS: Three RNA helicases, RNA helicase A, Upf1 and Mov10, were identified in Stau2-containing complexes. We focused our studies on Upf1, a key player in nonsense-mediated mRNA decay...
November 16, 2011: BMC Molecular Biology
Marjolaine Maher-Laporte, Frédéric Berthiaume, Mireille Moreau, Louis-André Julien, Gabriel Lapointe, Michael Mourez, Luc DesGroseillers
Messenger ribonucleoprotein particles (mRNPs) are used to transport mRNAs along neuronal dendrites to their site of translation. Numerous mRNA-binding and regulatory proteins within mRNPs finely regulate the fate of bound-mRNAs. Their specific combination defines different types of mRNPs that in turn are related to specific synaptic functions. One of these mRNA-binding proteins, Staufen2 (Stau2), was shown to transport dendritic mRNAs along microtubules. Its knockdown expression in neurons was shown to change spine morphology and synaptic functions...
June 28, 2010: PloS One
Marjolaine Maher-Laporte, Luc DesGroseillers
Messenger ribonucleoprotein particles (mRNPs) are used to transport mRNAs along neuronal dendrites to their site of translation. Staufen2 is an mRNA-binding protein expressed in the cell bodies and cellular processes of different brain cells. It is notably involved in the transport of dendritic mRNAs along microtubules. Its knockdown expression was shown to change spine morphology and impair synaptic functions. However, the identity of Staufen2-bound mRNAs in brain cells is still completely unknown. As a mean to identify these mRNAs, we immunoprecipitated Staufen2-containing mRNPs from embryonic rat brains and used a genome wide approach to identify Staufen2-associated mRNAs...
May 2010: BMB Reports
Jun-Young Oh, Yeon-Ju Nam, Anna Jo, Hyo-Soon Cheon, Sang-Myung Rhee, Joong-Ki Park, Jin-A Lee, Hyong Kyu Kim
Although the dendritic localization and translation of a subset of mRNAs plays a pivotal role in synaptic plasticity, the dendritic mRNAs and their functions have been only minimally characterized thus far. In this study, we isolated mRNAs from Staufen2-containing ribonucleoprotein complexes, which function as modules for the transport of mRNA to the dendrites, and then constructed a cDNA library. Apolipoprotein E gene (APOE) mRNA was isolated from the dendritic mRNA-specific cDNA library. The specific localization of APOE mRNA was evaluated via in situ hybridization...
August 2010: Journal of Neurochemistry
Yeon-Ju Nam, Hyo-Soon Cheon, Young-Ki Choi, Seok-Yong Kim, Eun-Young Shin, Eung-Gook Kim, Hyong Kyu Kim
Although transport and subsequent translation of dendritic mRNA play an important role in neuronal synaptic plasticity, the underlying mechanisms for modulating dendritic mRNA transport are almost completely unknown. In this study, we identified and characterized an interaction between Staufen2 and mitogen-activated protein kinase (MAPK) with co-immunoprecipitation assays. Staufen2 utilized a docking (D) site to interact with ERK1/2; deleting the D-site decreased colocalization of Staufen2 with immunoreactive ERK1/2 in the cell body regions of cultured hippocampal neurons, and it reduced the amount of Staufen2-containing RNP complexes in the distal dendrites...
August 8, 2008: Biochemical and Biophysical Research Communications
Luc Furic, Marjolaine Maher-Laporte, Luc DesGroseillers
Messenger RNAs are associated with multiple RNA-binding proteins to form ribonucleoprotein (mRNP) complexes. These proteins are important regulators of the fate of their target mRNAs. In human cells, Staufen1 and Staufen2 proteins, coded by two different genes, are double-stranded RNA-binding proteins involved in several cellular functions including mRNA localization, translation, and decay. Although 51% identical, these proteins are nevertheless found in different RNA particles. In addition, differential splicing events generate Staufen2 isoforms that only differ at their N-terminal extremities...
February 2008: RNA
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