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  1. Article ; Online: New frontiers in RNA transport and local translation in neurons.

    Van Driesche, Sarah J / Martin, Kelsey C

    Developmental neurobiology

    2018  Volume 78, Issue 3, Page(s) 331–339

    Abstract: RNA localization to neuronal dendrites and axons is increasingly recognized as a significant and widespread mechanism of gene expression control in neurons. High-throughput RNA sequencing is rapidly expanding the universe of known localized mRNAs. ... ...

    Abstract RNA localization to neuronal dendrites and axons is increasingly recognized as a significant and widespread mechanism of gene expression control in neurons. High-throughput RNA sequencing is rapidly expanding the universe of known localized mRNAs. Although there are inherent difficulties in preparing sequencing libraries from dendrites and axons in the context of intact brain, genetic labeling strategies have paved the way for improved studies of this type. As the list of localized mRNAs grows, there is increasing need for functional validation of localized transcripts-that is, do particular localized transcripts serve demonstrable physiologic functions in axons or dendrites? Finally, specific details about what localized mRNAs do once they reach distal processes have long been elusive. Recent work using single-molecule imaging and other techniques is starting to fill in the picture of how transcripts navigate the localized environment and undergo activity-dependent translational de-repression. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 331-339, 2018.
    MeSH term(s) Animals ; Neurons/metabolism ; RNA Transport/physiology
    Language English
    Publishing date 2018-01-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2256184-5
    ISSN 1932-846X ; 1097-4695 ; 1932-8451 ; 0022-3034
    ISSN (online) 1932-846X ; 1097-4695
    ISSN 1932-8451 ; 0022-3034
    DOI 10.1002/dneu.22574
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory.

    Sawicka, Kirsty / Hale, Caryn R / Park, Christopher Y / Fak, John J / Gresack, Jodi E / Van Driesche, Sarah J / Kang, Jin Joo / Darnell, Jennifer C / Darnell, Robert B

    eLife

    2019  Volume 8

    Abstract: Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease ... ...

    Abstract Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease pathophysiology. Here we use conditional tagging of FMRP and CLIP (FMRP cTag CLIP) to examine FMRP mRNA targets in hippocampal CA1 pyramidal neurons, a critical cell type for learning and memory relevant to FXS phenotypes. Integrating these data with analysis of ribosome-bound transcripts in these neurons revealed CA1-enriched binding of autism-relevant mRNAs, and CA1-specific regulation of transcripts encoding circadian proteins. This contrasted with different targets in cerebellar granule neurons, and was consistent with circadian defects in hippocampus-dependent memory in
    MeSH term(s) Animals ; Autistic Disorder/genetics ; Autistic Disorder/metabolism ; Autistic Disorder/physiopathology ; CA1 Region, Hippocampal/cytology ; CA1 Region, Hippocampal/metabolism ; Cerebellum/cytology ; Cerebellum/metabolism ; Circadian Clocks/genetics ; Circadian Clocks/physiology ; Disease Models, Animal ; Fragile X Mental Retardation Protein/genetics ; Fragile X Mental Retardation Protein/metabolism ; Fragile X Syndrome/genetics ; Fragile X Syndrome/metabolism ; Fragile X Syndrome/physiopathology ; Gene Expression Regulation ; Humans ; Memory Disorders/genetics ; Memory Disorders/metabolism ; Memory Disorders/physiopathology ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism ; Pyramidal Cells/metabolism
    Chemical Substances Fragile X Mental Retardation Protein (139135-51-6)
    Language English
    Publishing date 2019-12-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.46919
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism.

    Darnell, Jennifer C / Van Driesche, Sarah J / Zhang, Chaolin / Hung, Ka Ying Sharon / Mele, Aldo / Fraser, Claire E / Stone, Elizabeth F / Chen, Cynthia / Fak, John J / Chi, Sung Wook / Licatalosi, Donny D / Richter, Joel D / Darnell, Robert B

    Cell

    2011  Volume 146, Issue 2, Page(s) 247–261

    Abstract: FMRP loss of function causes Fragile X syndrome (FXS) and autistic features. FMRP is a polyribosome-associated neuronal RNA-binding protein, suggesting that it plays a key role in regulating neuronal translation, but there has been little consensus ... ...

    Abstract FMRP loss of function causes Fragile X syndrome (FXS) and autistic features. FMRP is a polyribosome-associated neuronal RNA-binding protein, suggesting that it plays a key role in regulating neuronal translation, but there has been little consensus regarding either its RNA targets or mechanism of action. Here, we use high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) to identify FMRP interactions with mouse brain polyribosomal mRNAs. FMRP interacts with the coding region of transcripts encoding pre- and postsynaptic proteins and transcripts implicated in autism spectrum disorders (ASD). We developed a brain polyribosome-programmed translation system, revealing that FMRP reversibly stalls ribosomes specifically on its target mRNAs. Our results suggest that loss of a translational brake on the synthesis of a subset of synaptic proteins contributes to FXS. In addition, they provide insight into the molecular basis of the cognitive and allied defects in FXS and ASD and suggest multiple targets for clinical intervention.
    MeSH term(s) Animals ; Autistic Disorder/metabolism ; Autistic Disorder/physiopathology ; Brain/metabolism ; Fragile X Mental Retardation Protein/genetics ; Fragile X Mental Retardation Protein/metabolism ; Fragile X Syndrome/metabolism ; Fragile X Syndrome/physiopathology ; Humans ; Mice ; Mice, Knockout ; Polyribosomes/metabolism ; Protein Biosynthesis ; RNA-Binding Proteins ; Ribosomes/metabolism ; Sequence Analysis, RNA ; Synapses/metabolism
    Chemical Substances Fmr1 protein, mouse ; RNA-Binding Proteins ; Fragile X Mental Retardation Protein (139135-51-6)
    Language English
    Publishing date 2011-07-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2011.06.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism

    Darnell, Jennifer C. / Van Driesche, Sarah J. / Zhang, Chaolin / Hung, Ka Ying Sharon / Mele, Aldo / Fraser, Claire E. / Stone, Elizabeth F. / Chen, Cynthia / Fak, John J. / Chi, Sung Wook / Licatalosi, Donny D. / Richter, Joel D. / Darnell, Robert B.

    Cell

    Volume v. 146,, Issue no. 2

    Abstract: FMRP loss of function causes Fragile X syndrome (FXS) and autistic features. FMRP is a polyribosome-associated neuronal RNA-binding protein, suggesting that it plays a key role in regulating neuronal translation, but there has been little consensus ... ...

    Abstract FMRP loss of function causes Fragile X syndrome (FXS) and autistic features. FMRP is a polyribosome-associated neuronal RNA-binding protein, suggesting that it plays a key role in regulating neuronal translation, but there has been little consensus regarding either its RNA targets or mechanism of action. Here, we use high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) to identify FMRP interactions with mouse brain polyribosomal mRNAs. FMRP interacts with the coding region of transcripts encoding pre- and postsynaptic proteins and transcripts implicated in autism spectrum disorders (ASD). We developed a brain polyribosome-programmed translation system, revealing that FMRP reversibly stalls ribosomes specifically on its target mRNAs. Our results suggest that loss of a translational brake on the synthesis of a subset of synaptic proteins contributes to FXS. In addition, they provide insight into the molecular basis of the cognitive and allied defects in FXS and ASD and suggest multiple targets for clinical intervention.
    Keywords binding proteins ; messenger RNA ; RNA-binding proteins ; crosslinking ; ribosomes ; high-throughput nucleotide sequencing ; translation (genetics) ; mice ; precipitin tests ; autism ; mechanism of action ; cognition ; proteins ; brain
    Language English
    Document type Article
    ISSN 0092-8674
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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