Telomere Science Library

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about the Nobel-Prize Winning Science of Telomere Biology

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

Authors: Peisu P. Zhang, Kotb K. Abdelmohsen, Yong Y. Liu, Kumiko K. Tominaga-Yamanaka, Je-Hyun JH. Yoon, Grammatikakis G. Ioannis, Jennifer L JL. Martindale, Yongqing Y. Zhang, Kevin G KG. Becker, In Hong IH. Yang, Myriam M. Gorospe, Mark P MP. Mattson
Published: 11/20/2015, Nature communications


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.

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