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  • 1
    Online Resource
    Online Resource
    Rockefeller University Press ; 2011
    In:  Journal of Cell Biology Vol. 194, No. 3 ( 2011-08-08), p. 441-457
    In: Journal of Cell Biology, Rockefeller University Press, Vol. 194, No. 3 ( 2011-08-08), p. 441-457
    Abstract: In neurons, regulation of gene expression occurs in part through translational control at the synapse. A fundamental requirement for such local control is the targeted delivery of select neuronal mRNAs and regulatory RNAs to distal dendritic sites. The nature of spatial RNA destination codes, and the mechanism by which they are interpreted for dendritic delivery, remain poorly understood. We find here that in a key dendritic RNA transport pathway (exemplified by BC1 RNA, a dendritic regulatory RNA, and protein kinase M ζ [PKMζ] mRNA, a dendritic mRNA), noncanonical purine•purine nucleotide interactions are functional determinants of RNA targeting motifs. These motifs are specifically recognized by heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), a trans-acting factor required for dendritic delivery. Binding to hnRNP A2 and ensuing dendritic delivery are effectively competed by RNAs with CGG triplet repeat expansions. CGG repeats, when expanded in the 5′ untranslated region of fragile X mental retardation 1 (FMR1) mRNA, cause fragile X–associated tremor/ataxia syndrome. The data suggest that cellular dysregulation observed in the presence of CGG repeat RNA may result from molecular competition in neuronal RNA transport pathways.
    Type of Medium: Online Resource
    ISSN: 1540-8140 , 0021-9525
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    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2011
    detail.hit.zdb_id: 1421310-2
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2006
    In:  Journal of Molecular Biology Vol. 356, No. 5 ( 2006-3), p. 1118-1123
    In: Journal of Molecular Biology, Elsevier BV, Vol. 356, No. 5 ( 2006-3), p. 1118-1123
    Type of Medium: Online Resource
    ISSN: 0022-2836
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2006
    detail.hit.zdb_id: 1355192-9
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Society for Neuroscience ; 2009
    In:  The Journal of Neuroscience Vol. 29, No. 32 ( 2009-08-12), p. 9977-9986
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 29, No. 32 ( 2009-08-12), p. 9977-9986
    Abstract: Regulatory RNAs have been suggested to contribute to the control of gene expression in eukaryotes. Brain cytoplasmic (BC) RNAs are regulatory RNAs that control translation initiation. We now report that neuronal BC1 RNA plays an instrumental role in the protein-synthesis-dependent implementation of neuronal excitation–repression equilibria. BC1 repression counter-regulates translational stimulation resulting from synaptic activation of group I metabotropic glutamate receptors (mGluRs). Absence of BC1 RNA precipitates plasticity dysregulation in the form of neuronal hyperexcitability, elicited by group I mGluR-stimulated translation and signaled through the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway. Dysregulation of group I mGluR function in the absence of BC1 RNA gives rise to abnormal brain function. Cortical EEG recordings from freely moving BC1 −/− animals show that group I mGluR-mediated oscillations in the gamma frequency range are significantly elevated. When subjected to sensory stimulation, these animals display an acute group I mGluR-dependent propensity for convulsive seizures. Inadequate RNA control in neurons is thus causally linked to heightened group I mGluR-stimulated translation, neuronal hyperexcitability, heightened gamma band oscillations, and epileptogenesis. These data highlight the significance of small RNA control in neuronal plasticity.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2009
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    SAGE Publications ; 2004
    In:  The Neuroscientist Vol. 10, No. 5 ( 2004-10), p. 456-466
    In: The Neuroscientist, SAGE Publications, Vol. 10, No. 5 ( 2004-10), p. 456-466
    Abstract: The strength of synaptic connections can undergo long-lasting changes, and such long-term plasticity is thought to underlie higher brain functions such as learning and memory. De novo synthesis of proteins is required for such plastic changes. This model is now supported by several lines of experimental data. Components of translational machinery have been identified in dendrites, including ribosomes, translational factors, numerous RNAs, and components of posttranslational secretory pathways. Various RNAs have been shown to be actively and rapidly transported to dendrites. Dendritic RNAs typically contain transport-specifying elements (dendritic targeting elements). Such dendritic targeting elements associate with transacting factors to form transport-competent ribonucleoprotein particles. It is assumed that molecular motors mediate transport of such particles along dendritic cytoskeletal elements. Once an mRNA has arrived at its dendritic destination site, appropriate spatiotemporal control of its translation, for example, in response to transsynaptic activity, becomes vital. Such local translational control, recent evidence indicates, is implemented at different levels and through various pathways. In the default state, translation is assumed to be repressed, and several mechanisms, some including small untranslated RNAs, have been proposed to contribute to such repression. Translational control at the synapse thus provides a molecular basis for the long-term, input-specific modulation of synaptic strength.
    Type of Medium: Online Resource
    ISSN: 1073-8584 , 1089-4098
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2004
    detail.hit.zdb_id: 2029471-2
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  • 5
    Online Resource
    Online Resource
    Life Science Alliance, LLC ; 2022
    In:  Life Science Alliance Vol. 5, No. 12 ( 2022-12), p. e202201496-
    In: Life Science Alliance, Life Science Alliance, LLC, Vol. 5, No. 12 ( 2022-12), p. e202201496-
    Abstract: Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood–brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus.
    Type of Medium: Online Resource
    ISSN: 2575-1077
    Language: English
    Publisher: Life Science Alliance, LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2948687-7
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  • 6
    Online Resource
    Online Resource
    SAGE Publications ; 2018
    In:  Journal of Investigative Medicine Vol. 66, No. 7 ( 2018-10), p. 1055-1063
    In: Journal of Investigative Medicine, SAGE Publications, Vol. 66, No. 7 ( 2018-10), p. 1055-1063
    Abstract: Regulatory brain cytoplasmic 200 RNA (BC200 RNA) is highly expressed in human mammary carcinoma cells. Here, we ask whether BC200 RNA becomes detectable in peripheral blood of patients with invasive breast cancer. Using quantitative reverse-transcription PCR (qRT-PCR) methodology, we observed that BC200 RNA blood levels were significantly elevated, in comparison with healthy subjects, in patients with invasive breast cancer prior to tumorectomy (p=0.001) and in patients with metastatic breast cancer (p=0.003). In patients with invasive breast cancer who had recently undergone tumorectomy, BC200 RNA blood levels were not distinguishable from levels in healthy subjects. However, normality analysis revealed a heterogeneous distribution of patients in this group, including a subgroup of individuals with high residual BC200 RNA blood levels. In blood from patients with invasive breast cancer, BC200 RNA was specifically detected in the mononuclear leukocyte fraction. The qRT-PCR approach is sensitive enough to detect as few as three BC200 RNA-expressing tumor cells. Our work establishes the potential of BC200 RNA detection in blood to serve as a molecular indicator of invasive breast malignancy.
    Type of Medium: Online Resource
    ISSN: 1081-5589 , 1708-8267
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2004
    In:  Journal of Biological Chemistry Vol. 279, No. 50 ( 2004-12), p. 52613-52622
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 279, No. 50 ( 2004-12), p. 52613-52622
    Type of Medium: Online Resource
    ISSN: 0021-9258
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 13 ( 2001-06-19), p. 6997-6998
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 13 ( 2001-06-19), p. 6997-6998
    Abstract: Intracellular transport and localization of cellular components are essential for the functional organization and plasticity of eukaryotic cells. Although the elucidation of protein transport mechanisms has made impressive progress in recent years, intracellular transport of RNA remains less well understood. The National Academy of Sciences Colloquium on Molecular Kinesis in Cellular Function and Plasticity therefore was devised as an interdisciplinary platform for participants to discuss intracellular molecular transport from a variety of different perspectives. Topics covered at the meeting included RNA metabolism and transport, mechanisms of protein synthesis and localization, the formation of complex interactive protein ensembles, and the relevance of such mechanisms for activity-dependent regulation and synaptic plasticity in neurons. It was the overall objective of the colloquium to generate momentum and cohesion for the emerging research field of molecular kinesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2008
    In:  Proceedings of the National Academy of Sciences Vol. 105, No. 22 ( 2008-06-03)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 22 ( 2008-06-03)
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2008
    In:  Proceedings of the National Academy of Sciences Vol. 105, No. 2 ( 2008-01-15), p. 734-739
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 2 ( 2008-01-15), p. 734-739
    Abstract: The fragile X mental retardation protein (FMRP), the functional absence of which causes fragile X syndrome, is an RNA-binding protein that has been implicated in the regulation of local protein synthesis at the synapse. The mechanism of FMRP's interaction with its target mRNAs, however, has remained controversial. In one model, it has been proposed that BC1 RNA, a small non-protein-coding RNA that localizes to synaptodendritic domains, operates as a requisite adaptor by specifically binding to both FMRP and, via direct base-pairing, to FMRP target mRNAs. Other models posit that FMRP interacts with its target mRNAs directly, i.e., in a BC1-independent manner. Here five laboratories independently set out to test the BC1–FMRP model. We report that specific BC1–FMRP interactions could be documented neither in vitro nor in vivo . Interactions between BC1 RNA and FMRP target mRNAs were determined to be of a nonspecific nature. Significantly, the association of FMRP with bona fide target mRNAs was independent of the presence of BC1 RNA in vivo . The combined experimental evidence is discordant with a proposed scenario in which BC1 RNA acts as a bridge between FMRP and its target mRNAs and rather supports a model in which BC1 RNA and FMRP are translational repressors that operate independently.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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