title: Staufen2 regulates neuronal target RNAs.
abstract: 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. Next, we show that Stau2 regulates steady-state levels of many neuronal RNAs and that its targets are predominantly downregulated in Stau2-deficient neurons. Detailed analysis confirms that Stau2 stabilizes the expression of one synaptic signaling component, the regulator of G protein signaling 4 (Rgs4) mRNA, via its 3' UTR. This study defines the global impact of Stau2 on mRNAs in neurons, revealing a role in stabilization of the levels of synaptic targets.
authors.affiliation: Department of Neuronal Cell Biology, Center for Brain Research, 1090 Vienna, Austria; Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.
authors.forename: Jacki E
authors.initials: JE
authors.lastname: Heraud-Farlow
authors.affiliation: Department of Anatomy and Cell Biology, Ludwig-Maximilians-University, 80336 Munich, Germany.
authors.forename: Tejaswini
authors.initials: T
authors.lastname: Sharangdhar
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; The Donnelly Centre, University of Toronto, Toronto, ON M5S 1E3, Canada.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neuronal Cell Biology, Center for Brain Research, 1090 Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Pfeifer
authors.affiliation: Department of Laboratory Medicine and Core Facility Genomics, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Tauber
authors.affiliation: Adolf Butenandt Institute, Ludwig-Maximilians-University, 80336 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 80336 Munich, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Orozco
authors.affiliation: Department of Neuronal Cell Biology, Center for Brain Research, 1090 Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hörmann
authors.affiliation: Department of Neuronal Cell Biology, Center for Brain Research, 1090 Vienna, Austria; Department of Anatomy and Cell Biology, Ludwig-Maximilians-University, 80336 Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Department of Neuronal Cell Biology, Center for Brain Research, 1090 Vienna, Austria.
authors.forename: Anetta
authors.initials: A
authors.lastname: Bakosova
authors.affiliation: Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Farlow
authors.affiliation: Adolf Butenandt Institute, Ludwig-Maximilians-University, 80336 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 80336 Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), 80336 Munich, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Edbauer
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Lipshitz
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; The Donnelly Centre, University of Toronto, Toronto, ON M5S 1E3, Canada.
authors.forename: Quaid D
authors.initials: QD
authors.lastname: Morris
authors.affiliation: Department of Laboratory Medicine and Core Facility Genomics, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.affiliation: Department of Neuronal Cell Biology, Center for Brain Research, 1090 Vienna, Austria. Electronic address: michael.doyle@meduniwien.ac.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Doyle
authors.affiliation: Department of Neuronal Cell Biology, Center for Brain Research, 1090 Vienna, Austria; Department of Anatomy and Cell Biology, Ludwig-Maximilians-University, 80336 Munich, Germany. Electronic address: michael.kiebler@med.uni-muenchen.de.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kiebler
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020413:3' Untranslated Regions; D020710:RGS Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C492188:Stau2 protein, rat; C098799:RGS4 protein