In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements

Chandrasekhar S. Raju, Nanaho Fukuda, Carmen López-Iglesias, Christian Göritz, Neus Visa, Piergiorgio Percipalle

    Research output: Contribution to journalArticle

    Abstract

    In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton- associated protein (Arc), brain-derived neurotrophic factor (BDNF), and calmodulin-dependent protein kinase II (CaMKIIα) mRNAs. We discovered that, in the adult mouse brain, CBF-A has a broad distribution. In the nucleus, CBF-A was found at active transcription sites and interchromosomal spaces and close to nuclear pores. In the cytoplasm, CBF-A localized to dendrites as well as pre- and postsynaptic sites. CBF-A was found in synaptosomal fractions, associated with Arc, BDNF, and CaMKIIα mRNAs. Electrophoretic mobility shift assays demonstrated a direct interaction mediated via their hnRNP A2 response element (A2RE)/RNA trafficking sequence (RTS) elements located in the 3′ untranslated regions. In situ hybridization and microscopy on live hippocampal neurons showed that CBF-A is in dynamic granules containing Arc, BDNF, and CaMKIIα mRNAs. N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) postsynaptic receptor stimulation led to CBF-A accumulation in dendrites; increased Arc, BDNF, and CaMKIIα mRNA levels; and increased amounts of transcripts coprecipitating with CBF-A. Finally, CBF-A gene knockdown led to decreased mRNA levels. We propose that CBF-A cotranscriptionally binds RTSs in Arc, BDNF, and CaMKIIα mRNAs and follows the transcripts from genes to dendrites, promoting activity-dependent nuclear sorting of transport-competent mRNAs.

    Original languageEnglish (US)
    Pages (from-to)1864-1877
    Number of pages14
    JournalMolecular Biology of the Cell
    Volume22
    Issue number11
    DOIs
    StatePublished - Jun 1 2011

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    Response Elements
    varespladib methyl
    Calcium-Calmodulin-Dependent Protein Kinase Type 2
    Brain-Derived Neurotrophic Factor
    Neurons
    Messenger RNA
    Dendrites
    Heterogeneous-Nuclear Ribonucleoproteins
    Gene Knockdown Techniques
    Isoxazoles
    Nuclear Pore
    AMPA Receptors
    Cell Nucleus Active Transport
    Drosophila serpent protein
    Propionates
    3' Untranslated Regions
    Electrophoretic Mobility Shift Assay
    Cytoskeleton
    Aspartic Acid
    Hydroxyl Radical

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

    Cite this

    In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements. / Raju, Chandrasekhar S.; Fukuda, Nanaho; López-Iglesias, Carmen; Göritz, Christian; Visa, Neus; Percipalle, Piergiorgio.

    In: Molecular Biology of the Cell, Vol. 22, No. 11, 01.06.2011, p. 1864-1877.

    Research output: Contribution to journalArticle

    Raju, Chandrasekhar S. ; Fukuda, Nanaho ; López-Iglesias, Carmen ; Göritz, Christian ; Visa, Neus ; Percipalle, Piergiorgio. / In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements. In: Molecular Biology of the Cell. 2011 ; Vol. 22, No. 11. pp. 1864-1877.
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