title: Novel RNA- and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity.
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.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Peisu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tominaga-Yamanaka
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Grammatikakis
authors.initials: G
authors.lastname: Ioannis
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, Singapore 117465, Singapore.|SINAPSE, National University of Singapore, Singapore 117465, Singapore.
authors.forename: In Hong
authors.initials: IH
authors.lastname: Yang
authors.affiliation: Laboratory of Genetics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; C497684:Fmr1 protein, mouse; C534796:TRF2 protein, mouse