Remote Control of Gene Function by Local Translation

The subcellular position of a protein is a key determinant of its function. Mounting evidence indicates that RNA localization, where specific mRNAs are transported subcellularly and subsequently translated in response to localized signals, is an evolutionarily conserved mechanism to control protein localization. On-site synthesis confers novel signaling properties to a protein and helps to maintain local proteome homeostasis. Local translation plays particularly important roles in distal neuronal compartments, and dysregulated RNA localization and translation cause defects in neuronal wiring and survival. Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function.

[1]  D. Purpura,et al.  Signals, Synapses, and Synthesis: How New Proteins Control Plasticity , 2009, Front. Neural Circuits.

[2]  A. Spang,et al.  Cotranslational transport of ABP140 mRNA to the distal pole of S. cerevisiae , 2011, The EMBO journal.

[3]  Uwe Ohler,et al.  FMR1 targets distinct mRNA sequence elements to regulate protein expression , 2012, Nature.

[4]  J. Fawcett,et al.  Axonal Protein Synthesis and Degradation Are Necessary for Efficient Growth Cone Regeneration , 2005, The Journal of Neuroscience.

[5]  A. Aschrafi,et al.  Axonal protein synthesis and the regulation of local mitochondrial function. , 2009, Results and problems in cell differentiation.

[6]  M. Selbach,et al.  Global quantification of mammalian gene expression control , 2011, Nature.

[7]  E. Klann,et al.  mTOR signaling: At the crossroads of plasticity, memory and disease , 2010, Trends in Neurosciences.

[8]  G. Korza,et al.  Multiplexed dendritic targeting of alpha calcium calmodulin-dependent protein kinase II, neurogranin, and activity-regulated cytoskeleton-associated protein RNAs by the A2 pathway. , 2008, Molecular biology of the cell.

[9]  G. Millot,et al.  Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway , 2013, Proceedings of the National Academy of Sciences.

[10]  S. M. Shenoy,et al.  Neurotrophin-Induced Transport of a β-Actin mRNP Complex Increases β-Actin Levels and Stimulates Growth Cone Motility , 2001, Neuron.

[11]  Junhyong Kim,et al.  Cytoplasmic Intron Sequence-Retaining Transcripts Can Be Dendritically Targeted via ID Element Retrotransposons , 2011, Neuron.

[12]  Joel D. Richter,et al.  Cytoplasmic Polyadenylation in Development and Beyond , 1999, Microbiology and Molecular Biology Reviews.

[13]  J. Fallon,et al.  The FXG: A Presynaptic Fragile X Granule Expressed in a Subset of Developing Brain Circuits , 2009, The Journal of Neuroscience.

[14]  E. Schuman,et al.  Dendritic Protein Synthesis, Synaptic Plasticity, and Memory , 2006, Cell.

[15]  R. Wysocki,et al.  Molecular Profiling of Activated Neurons by Phosphorylated Ribosome Capture , 2012, Cell.

[16]  Kenneth S Kosik,et al.  Neuronal RNA Granules A Link between RNA Localization and Stimulation-Dependent Translation , 2001, Neuron.

[17]  K. Kosik,et al.  Sorting of β-Actin mRNA and Protein to Neurites and Growth Cones in Culture , 1998, The Journal of Neuroscience.

[18]  C. Holt,et al.  Asymmetrical β-actin mRNA translation in growth cones mediates attractive turning to netrin-1 , 2006, Nature Neuroscience.

[19]  Giovanni Coppola,et al.  Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization. , 2011, RNA.

[20]  K. Keiler,et al.  RNA localization in bacteria. , 2011, Current opinion in microbiology.

[21]  K. Martin,et al.  Synapse- and Stimulus-Specific Local Translation During Long-Term Neuronal Plasticity , 2009, Science.

[22]  G. Superti-Furga,et al.  Interactome of two diverse RNA granules links mRNA localization to translational repression in neurons. , 2013, Cell reports.

[23]  C. Holt,et al.  Endocytosis-dependent desensitization and protein synthesis–dependent resensitization in retinal growth cone adaptation , 2005, Nature Neuroscience.

[24]  F. Müller,et al.  Splicing Segregation: The Minor Spliceosome Acts outside the Nucleus and Controls Cell Proliferation , 2007, Cell.

[25]  K. Broadie,et al.  The Ubiquitin Proteasome System Acutely Regulates Presynaptic Protein Turnover and Synaptic Efficacy , 2003, Current Biology.

[26]  C. Proud,et al.  The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). , 2008, Frontiers in bioscience : a journal and virtual library.

[27]  Evan Z. Macosko,et al.  Local translation of RhoA regulates growth cone collapse , 2005, Nature.

[28]  Michael Benatar,et al.  Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS , 2013, Nature.

[29]  C. Bramham,et al.  Dendritic mRNA: transport, translation and function , 2007, Nature Reviews Neuroscience.

[30]  J. Lykke-Andersen,et al.  Cytoplasmic mRNP granules at a glance , 2011, Journal of Cell Science.

[31]  K. Nader,et al.  eIF2α Phosphorylation Bidirectionally Regulates the Switch from Short- to Long-Term Synaptic Plasticity and Memory , 2007, Cell.

[32]  A. Riccio,et al.  An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons , 2010, Nature Neuroscience.

[33]  Mark F. Bear,et al.  The Autistic Neuron: Troubled Translation? , 2008, Cell.

[34]  I. Moll,et al.  Ribosome heterogeneity: another level of complexity in bacterial translation regulation , 2013, Current opinion in microbiology.

[35]  A. Gingras,et al.  A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Oswald Steward,et al.  Synaptic Activation Causes the mRNA for the IEG Arc to Localize Selectively near Activated Postsynaptic Sites on Dendrites , 1998, Neuron.

[37]  H. Okano,et al.  Neural RNA-Binding Protein Musashi1 Controls Midline Crossing of Precerebellar Neurons through Posttranscriptional Regulation of Robo3/Rig-1 Expression , 2010, Neuron.

[38]  S. Warren,et al.  Local RNA Translation at the Synapse and in Disease , 2011, The Journal of Neuroscience.

[39]  J. Rehwinkel,et al.  mRNA quality control: An ancient machinery recognizes and degrades mRNAs with nonsense codons , 2007, FEBS letters.

[40]  T. Jessell,et al.  A Homeodomain Protein Code Specifies Progenitor Cell Identity and Neuronal Fate in the Ventral Neural Tube , 2000, Cell.

[41]  Michael Piper,et al.  Subcellular Profiling Reveals Distinct and Developmentally Regulated Repertoire of Growth Cone mRNAs , 2010, The Journal of Neuroscience.

[42]  J. Yates,et al.  Arginylation of ß-Actin Regulates Actin Cytoskeleton and Cell Motility , 2006, Science.

[43]  P. Tomançak,et al.  Global Analysis of mRNA Localization Reveals a Prominent Role in Organizing Cellular Architecture and Function , 2007, Cell.

[44]  M. L. Montesinos,et al.  Deregulated mTOR-mediated translation in intellectual disability , 2012, Progress in Neurobiology.

[45]  D. Baulcombe Small RNA—the Secret of Noble Rot , 2013, Science.

[46]  Xun Hu,et al.  Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6 , 2009, Science.

[47]  Henry M. Fales,et al.  Reversible Glutathionylation Regulates Actin Polymerization in A431 Cells* , 2001, The Journal of Biological Chemistry.

[48]  A. Hinnebusch Evidence for translational regulation of the activator of general amino acid control in yeast. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Y. Pilpel,et al.  Axonal transcription factors signal retrogradely in lesioned peripheral nerve , 2012, The EMBO journal.

[50]  George M. Church,et al.  Highly Multiplexed Subcellular RNA Sequencing in Situ , 2014, Science.

[51]  Christos G. Gkogkas,et al.  Autism-related deficits via dysregulated eIF4E-dependent translational control , 2012, Nature.

[52]  J. Steitz,et al.  Minor-class splicing occurs in the nucleus of the Xenopus oocyte. , 2008, RNA.

[53]  Simon L. Bullock,et al.  Single-molecule assays reveal that RNA localization signals regulate dynein-dynactin copy number on individual transcript cargoes , 2012, Nature Cell Biology.

[54]  P. Brown,et al.  Extensive Association of Functionally and Cytotopically Related mRNAs with Puf Family RNA-Binding Proteins in Yeast , 2004, PLoS biology.

[55]  Xun Hu,et al.  TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis , 2008, Science.

[56]  J. Condeelis,et al.  Localization of all seven messenger RNAs for the actin-polymerization nucleator Arp2/3 complex in the protrusions of fibroblasts , 2005, Journal of Cell Science.

[57]  M. Morgan,et al.  New initiation factor activity required for globin mRNA translation. , 1983, The Journal of biological chemistry.

[58]  E. Schuman,et al.  Ubiquitin-Mediated Proteasome Activity Is Required for Agonist-Induced Endocytosis of GluRs , 2003, Current Biology.

[59]  Y. Pilpel,et al.  Subcellular transcriptomics—Dissection of the mRNA composition in the axonal compartment of sensory neurons , 2014, Developmental neurobiology.

[60]  M. Schapira,et al.  Regulated translation initiation controls stress-induced gene expression in mammalian cells. , 2000, Molecular cell.

[61]  C. Holt,et al.  Chemotropic Responses of Retinal Growth Cones Mediated by Rapid Local Protein Synthesis and Degradation , 2001, Neuron.

[62]  Bo T. Porse,et al.  Regulation of Axon Guidance by Compartmentalized Nonsense-Mediated mRNA Decay , 2013, Cell.

[63]  D. Geschwind,et al.  Autism spectrum disorders: developmental disconnection syndromes , 2007, Current Opinion in Neurobiology.

[64]  Peter K. Todd,et al.  CGG Repeat-Associated Translation Mediates Neurodegeneration in Fragile X Tremor Ataxia Syndrome , 2013, Neuron.

[65]  Y. Goshima,et al.  Identification of axon‐enriched MicroRNAs localized to growth cones of cortical neurons , 2014, Developmental neurobiology.

[66]  Shifeng Xue,et al.  Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning , 2011, Cell.

[67]  K. Nader,et al.  Translational control of hippocampal synaptic plasticity and memory by the eIF2α kinase GCN2 , 2005, Nature.

[68]  A. Gingras,et al.  eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. , 1999, Annual review of biochemistry.

[69]  J L Haines,et al.  Supporting Online Material Materials and Methods Figs. S1 to S7 Tables S1 to S4 References Mutations in the Fus/tls Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis , 2022 .

[70]  A. Fire,et al.  Specific interference by ingested dsRNA , 1998, Nature.

[71]  B. Oostra,et al.  The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses , 2003, Cell.

[72]  D. Sabatini,et al.  mTOR Signaling in Growth Control and Disease , 2012, Cell.

[73]  Mani Ramaswami,et al.  Altered Ribostasis: RNA-Protein Granules in Degenerative Disorders , 2013, Cell.

[74]  Byung C. Yoon,et al.  Local Translation of Extranuclear Lamin B Promotes Axon Maintenance , 2012, Cell.

[75]  Stuart L. Schreiber,et al.  A mammalian protein targeted by G1-arresting rapamycin–receptor complex , 1994, Nature.

[76]  H. Eng,et al.  Protein synthesis in axons and its possible functions , 2000, Journal of neurocytology.

[77]  L. Pon,et al.  Puf3p, a Pumilio family RNA binding protein, localizes to mitochondria and regulates mitochondrial biogenesis and motility in budding yeast , 2007, The Journal of cell biology.

[78]  L. Canclini,et al.  Glia to axon RNA transfer , 2014, Developmental neurobiology.

[79]  J. Monod,et al.  [Operon: a group of genes with the expression coordinated by an operator]. , 1960, Comptes rendus hebdomadaires des seances de l'Academie des sciences.

[80]  Jimin Pei,et al.  Cell-free Formation of RNA Granules: Bound RNAs Identify Features and Components of Cellular Assemblies , 2012, Cell.

[81]  A. Aschrafi,et al.  Regulation of axonal trafficking of cytochrome c oxidase IV mRNA , 2010, Molecular and Cellular Neuroscience.

[82]  C. Holt,et al.  Regulation of chemotropic guidance of nerve growth cones by microRNA , 2011, Molecular Brain.

[83]  Sanjay Tyagi,et al.  Neuronal mRNAs travel singly into dendrites , 2012, Proceedings of the National Academy of Sciences.

[84]  Bruno A. Cisterna,et al.  Morphological evidence for a transport of ribosomes from Schwann cells to regenerating axons , 2011, Glia.

[85]  J. Darnell,et al.  The translation of translational control by FMRP: therapeutic targets for FXS , 2013, Nature Neuroscience.

[86]  R. Singer,et al.  Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility. , 2001, Neuron.

[87]  D. Dinsdale,et al.  Sustained translational repression by eIF2α-P mediates prion neurodegeneration , 2012, Nature.

[88]  J. Lawrence,et al.  Intracellular localization of messenger RNAs for cytoskeletal proteins , 1986, Cell.

[89]  S. Jaffrey,et al.  Insights into the roles of local translation from the axonal transcriptome , 2012, Open Biology.

[90]  Konstantin A Lukyanov,et al.  Intra-axonal translation and retrograde trafficking of CREB promotes neuronal survival , 2008, Nature Cell Biology.

[91]  Kenta Hara,et al.  Brain-Derived Neurotrophic Factor Induces Mammalian Target of Rapamycin-Dependent Local Activation of Translation Machinery and Protein Synthesis in Neuronal Dendrites , 2004, The Journal of Neuroscience.

[92]  P. Lasko mRNA localization and translational control in Drosophila oogenesis. , 2012, Cold Spring Harbor perspectives in biology.

[93]  S. Jaffrey,et al.  Intra-axonal Translation of SMAD1/5/8 Mediates Retrograde Regulation of Trigeminal Ganglia Subtype Specification , 2012, Neuron.

[94]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[95]  J. Keene,et al.  Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs. , 1993, Molecular and cellular biology.

[96]  Amar N. Kar,et al.  MicroRNAs in the axon and presynaptic nerve terminal , 2013, Front. Cell. Neurosci..

[97]  John G. Flanagan,et al.  Transmembrane Receptor DCC Associates with Protein Synthesis Machinery and Regulates Translation , 2010, Cell.

[98]  F. Court,et al.  Schwann Cell to Axon Transfer of Ribosomes: Toward a Novel Understanding of the Role of Glia in the Nervous System , 2008, The Journal of Neuroscience.

[99]  N. Tsai,et al.  The adaptor Grb7 links netrin‐1 signaling to regulation of mRNA translation , 2007, The EMBO journal.

[100]  J. Alvarez The autonomous axon: a model based on local synthesis of proteins. , 2001, Biological research.

[101]  C. Albrecht,et al.  Translation of the cell adhesion molecule ALCAM in axonal growth cones – regulation and functional importance , 2012, Journal of Cell Science.

[102]  Yi-shuian Huang,et al.  Facilitation of dendritic mRNA transport by CPEB. , 2003, Genes & development.

[103]  R. Singer,et al.  Structural elements required for the localization of ASH1 mRNA and of a green fluorescent protein reporter particle in vivo , 1999, Current Biology.

[104]  K. Martin,et al.  The Ubiquitin Proteasome System Functions as an Inhibitory Constraint on Synaptic Strengthening , 2003, Current Biology.

[105]  Christopher Ricks,et al.  To J.S. , 2014 .

[106]  G. Cao,et al.  Cytoplasmic Polyadenylation Element Binding Protein 1-Mediated mRNA Translation in Purkinje Neurons Is Required for Cerebellar Long-Term Depression and Motor Coordination , 2007, The Journal of Neuroscience.

[107]  D. Kwiatkowski,et al.  Tuberous sclerosis. , 1994, Archives of dermatology.

[108]  Jaime Alvarez,et al.  Protein synthesis in axons and terminals: significance for maintenance, plasticity and regulation of phenotype With a critique of slow transport theory , 2000, Progress in Neurobiology.

[109]  Byung C. Yoon,et al.  Axonal mRNA localization and local protein synthesis in nervous system assembly, maintenance and repair , 2012, Nature Reviews Neuroscience.

[110]  Graydon B. Gonsalvez,et al.  RNA localization in yeast: moving towards a mechanism , 2005, Biology of the cell.

[111]  Brian B. Gibbens,et al.  Non-ATG–initiated translation directed by microsatellite expansions , 2010, Proceedings of the National Academy of Sciences.

[112]  Junhyong Kim,et al.  Cytoplasmic intron retention, function, splicing, and the sentinel RNA hypothesis , 2014, Wiley interdisciplinary reviews. RNA.

[113]  Wenlan Wang,et al.  RNA transport and localized protein synthesis in neurological disorders and neural repair , 2007, Developmental neurobiology.

[114]  Jiaqi Yao,et al.  An essential role for β-actin mRNA localization and translation in Ca2+-dependent growth cone guidance , 2006, Nature Neuroscience.

[115]  C. Holt,et al.  Subcellular mRNA Localization in Animal Cells and Why It Matters , 2009, Science.

[116]  Jimin Pei,et al.  Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels , 2012, Cell.

[117]  Mu-ming Poo,et al.  Localized Synaptic Potentiation by BDNF Requires Local Protein Synthesis in the Developing Axon , 2002, Neuron.

[118]  J. Condeelis,et al.  How and why does β‐actin mRNA target? , 2005 .

[119]  M. Gorospe HuR in the Mammalian Genotoxic Response: Post-Transcriptional Multitasking , 2003, Cell cycle.

[120]  G. Goodhill,et al.  A new chemotaxis assay shows the extreme sensitivity of axons to molecular gradients , 2004, Nature Neuroscience.

[121]  J. Dahlberg,et al.  Molecular biology. , 1977, Science.

[122]  M. Kiebler,et al.  Independent localization of MAP2, CaMKIIα and β-actin RNAs in low copy numbers , 2011, EMBO reports.

[123]  P. Chartrand,et al.  Nuclear shuttling of She2p couples ASH1 mRNA localization to its translational repression by recruiting Loc1p and Puf6p. , 2009, Molecular biology of the cell.

[124]  A. Hinnebusch,et al.  Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets , 2009, Cell.

[125]  K. Nakai,et al.  Prediction of subcellular locations of proteins: Where to proceed? , 2010, Proteomics.

[126]  C. Holt,et al.  Local translation and directional steering in axons , 2007, The EMBO journal.

[127]  Michael Piper,et al.  Signaling Mechanisms Underlying Slit2-Induced Collapse of Xenopus Retinal Growth Cones , 2006, Neuron.

[128]  G. Struhl,et al.  Cis- acting sequences responsible for anterior localization of bicoid mRNA in Drosophila embryos , 1988, Nature.

[129]  S. J. Smith,et al.  Multiple ubiquitin conjugates are present in rat brain synaptic membranes and postsynaptic densities , 1994, Neuroscience Letters.

[130]  G. Pavitt,et al.  Clues to the mechanism of action of eIF2B, the guanine-nucleotide-exchange factor for translation initiation. , 2008, Biochemical Society transactions.

[131]  Christine C. Hudson,et al.  Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. , 1997, Science.

[132]  J. Darnell,et al.  Fragile X Mental Retardation Protein Targets G Quartet mRNAs Important for Neuronal Function , 2001, Cell.

[133]  Nicholas T. Ingolia,et al.  Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling , 2009, Science.

[134]  Robert H Singer,et al.  A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. , 2008, Developmental cell.

[135]  Robert Walgate,et al.  Proliferation , 1985, Nature.

[136]  J. Condeelis,et al.  How and why does beta-actin mRNA target? , 2005, Biology of the cell.

[137]  C. Holt,et al.  The Central Dogma Decentralized: New Perspectives on RNA Function and Local Translation in Neurons , 2013, Neuron.

[138]  K. Swoboda,et al.  Escaping the Nuclear Confines: Signal-Dependent Pre-mRNA Splicing in Anucleate Platelets , 2005, Cell.

[139]  L. Parada,et al.  PTEN signaling in autism spectrum disorders , 2012, Current Opinion in Neurobiology.

[140]  P. Hollenbeck,et al.  Organization and translation of mRNA in sympathetic axons , 2003, Journal of Cell Science.

[141]  S. Thompson Tricks an IRES uses to enslave ribosomes. , 2012, Trends in microbiology.

[142]  S. Mili,et al.  Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions , 2008, Nature.

[143]  John R Yates,et al.  Arginylation of beta-actin regulates actin cytoskeleton and cell motility. , 2006, Science.

[144]  Jeffery L. Twiss,et al.  Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs , 2007, The Journal of cell biology.

[145]  J. Besharse,et al.  Immediate early response of the circadian polyA ribonuclease nocturnin to two extracellular stimuli. , 2007, RNA.

[146]  N. Sonenberg,et al.  Upstream and downstream of mTOR. , 2004, Genes & development.

[147]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[148]  Hye Yoon Park,et al.  Visualization of Dynamics of Single Endogenous mRNA Labeled in Live Mouse , 2014, Science.

[149]  M. Ehlers Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system , 2003, Nature neuroscience.

[150]  D. Melamed,et al.  Tom20 Mediates Localization of mRNAs to Mitochondria in a Translation-Dependent Manner , 2009, Molecular and Cellular Biology.

[151]  N. Sonenberg,et al.  Eukaryotic mRNA cap binding protein: purification by affinity chromatography on sepharose-coupled m7GDP. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[152]  C. Will,et al.  Minor spliceosome components are predominantly localized in the nucleus , 2008, Proceedings of the National Academy of Sciences.

[153]  K. Hoek,et al.  hnRNP A2 selectively binds the cytoplasmic transport sequence of myelin basic protein mRNA. , 1998, Biochemistry.

[154]  Lindy E. Barrett,et al.  RNA splicing capability of live neuronal dendrites. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[155]  R. Padgett,et al.  Rates of in situ transcription and splicing in large human genes , 2009, Nature Structural &Molecular Biology.

[156]  W. Sossin,et al.  A recollection of mTOR signaling in learning and memory. , 2013, Learning & memory.

[157]  K. Kosik,et al.  Sorting of beta-actin mRNA and protein to neurites and growth cones in culture. , 1998, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[158]  K. A. Lee,et al.  Involvement of eukaryotic initiation factor 4A in the cap recognition process. , 1983, The Journal of biological chemistry.

[159]  S. Tenenbaum,et al.  Eukaryotic mRNPs may represent posttranscriptional operons. , 2002, Molecular cell.

[160]  J. Heitman,et al.  Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast , 1991, Science.

[161]  E. Miska,et al.  Is There Social RNA? , 2013, Science.

[162]  E Westhof,et al.  RNA–RNA interaction is required for the formation of specific bicoid mRNA 3′ UTR–STAUFEN ribonucleoprotein particles , 1997, The EMBO journal.

[163]  Hwan‐Ching Tai,et al.  Axonal Translation of β-Catenin Regulates Synaptic Vesicle Dynamics , 2013, The Journal of Neuroscience.

[164]  J. Flanagan,et al.  Axonal Protein Synthesis Provides a Mechanism for Localized Regulation at an Intermediate Target , 2002, Cell.

[165]  Carl W. Cotman,et al.  Axonal mRNA in Uninjured and Regenerating Cortical Mammalian Axons , 2009, The Journal of Neuroscience.

[166]  Y. Oda,et al.  Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2alpha in Caenorhabditis elegans. , 2008, Genes & development.

[167]  Xiaoxiang Zheng,et al.  Autophagy in axonal and dendritic degeneration , 2013, Trends in Neurosciences.

[168]  G. Edelman,et al.  The ribosome filter hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[169]  R. Singer,et al.  Localization of a β-Actin Messenger Ribonucleoprotein Complex with Zipcode-Binding Protein Modulates the Density of Dendritic Filopodia and Filopodial Synapses , 2003, The Journal of Neuroscience.

[170]  O. Bozdagi,et al.  Axonal cap‐dependent translation regulates presynaptic p35 , 2014, Developmental neurobiology.

[171]  Bin Wu,et al.  Single β-Actin mRNA Detection in Neurons Reveals a Mechanism for Regulating Its Translatability , 2014, Science.

[172]  J. Mandel,et al.  G–quadruplex RNA structure as a signal for neurite mRNA targeting , 2011, EMBO reports.

[173]  S. Tenenbaum,et al.  Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[174]  W. Scheper,et al.  Activation of the Unfolded Protein Response Is an Early Event in Alzheimer’s and Parkinson’s Disease , 2012, Neurodegenerative Diseases.

[175]  A. Gingras,et al.  Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function , 1994, Nature.

[176]  J. L. Smith,et al.  RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization. , 1993, Development.

[177]  M. Molinari,et al.  Dendritic LSm1/CBP80-mRNPs mark the early steps of transport commitment and translational control , 2009, The Journal of cell biology.

[178]  D. Licatalosi,et al.  FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism , 2011, Cell.

[179]  P. Sarnow,et al.  Internal ribosome entry sites in eukaryotic mRNA molecules. , 2001, Genes & development.

[180]  Erin M. Schuman,et al.  The Local Transcriptome in the Synaptic Neuropil Revealed by Deep Sequencing and High-Resolution Imaging , 2012, Neuron.

[181]  Jon R Lorsch,et al.  The mechanism of eukaryotic translation initiation: new insights and challenges. , 2012, Cold Spring Harbor perspectives in biology.