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

Nat Commun. 2015 Nov 20;6:8888. doi: 10.1038/ncomms9888.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport
  • Axons / metabolism*
  • Biological Transport
  • Carrier Proteins
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism*

Substances

  • Carrier Proteins
  • Fmr1 protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • TRF2 protein, mouse
  • Telomeric Repeat Binding Protein 2
  • Fragile X Mental Retardation Protein

Associated data

  • GEO/GSE72887