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

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 and Mark P. Mattson ()
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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
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

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9888

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