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Novel RNA- and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity

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  • Peisu Zhang

    (Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Kotb Abdelmohsen

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Yong Liu

    (Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Kumiko Tominaga-Yamanaka

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Je-Hyun Yoon

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Grammatikakis Ioannis

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Jennifer L. Martindale

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Yongqing Zhang

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Kevin G. Becker

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • In Hong Yang

    (National University of Singapore
    SINAPSE, National University of Singapore)

  • Myriam Gorospe

    (Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA)

  • Mark P. Mattson

    (Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA
    Johns Hopkins University School of Medicine)

Abstract

Despite considerable evidence that RNA-binding proteins (RBPs) regulate mRNA transport and local translation in dendrites, roles for axonal RBPs are poorly understood. Here we demonstrate that a non-telomeric isoform of telomere repeat-binding factor 2 (TRF2-S) is a novel RBP that regulates axonal plasticity. TRF2-S interacts directly with target mRNAs to facilitate their axonal delivery. The process is antagonized by fragile X mental retardation protein (FMRP). Distinct from the current RNA-binding model of FMRP, we show that FMRP occupies the GAR domain of TRF2-S protein to block the assembly of TRF2-S–mRNA complexes. Overexpressing TRF2-S and silencing FMRP promotes mRNA entry to axons and enhances axonal outgrowth and neurotransmitter release from presynaptic terminals. Our findings suggest a pivotal role for TRF2-S in an axonal mRNA localization pathway that enhances axon outgrowth and neurotransmitter release.

Suggested Citation

  • Peisu Zhang & Kotb Abdelmohsen & Yong Liu & Kumiko Tominaga-Yamanaka & Je-Hyun Yoon & Grammatikakis Ioannis & Jennifer L. Martindale & Yongqing Zhang & Kevin G. Becker & In Hong Yang & Myriam Gorospe , 2015. "Novel RNA- and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity," Nature Communications, Nature, vol. 6(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9888
    DOI: 10.1038/ncomms9888
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