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, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number8888
JournalNature communications
Volume6
DOIs
StatePublished - Nov 20 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Novel RNA-and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity'. Together they form a unique fingerprint.

Cite this