Novel RNA- and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity
Copyright policy )Novel RNA- and FMRP-binding protein TRF2-S regulates axonal mRNA transport and presynaptic plasticity
AbstractDespite 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.
- National Institutes of Health United States
- National University of Singapore Libraries Singapore
- Johns Hopkins University School of Medicine United States
- Johns Hopkins Medicine United States
- National Institute of Health Pakistan
Male, genetic analysis, Axonal Transport, Rats, Sprague-Dawley, Fragile X Mental Retardation Protein, Mice, protein cross linking, cell growth, Telomeric Repeat Binding Protein 2, Fmr1 protein, Mice, Knockout, messenger RNA, adult, nuclear export signal, presynaptic nerve, protein domain, RNA-Binding Proteins, unclassified drug, female, fragile X mental retardation protein, Female, protein RNA binding, 570, animal experiment, protein assembly, Enterobacteria phage MS2, Article, animal tissue, dendrite, hippocampal neuronal culture, telomeric repeat binding factor 2, mitochondrial membrane, Animals, Humans, controlled study, human, nerve fiber, RNA, Messenger, protein motif, TRF2 protein, protein expression, mouse, multigene family, nonhuman, binding site, neurology, human cell, 500, Biological Transport, nerve cell plasticity, brain cell, RNA binding protein, TRF2 S protein, Axons, Rats, Mice, Inbred C57BL, alpha tubulin, carrier protein, cell differentiation, neurotransmitter release, plasticity, RNA, protein, Carrier Proteins
Male, genetic analysis, Axonal Transport, Rats, Sprague-Dawley, Fragile X Mental Retardation Protein, Mice, protein cross linking, cell growth, Telomeric Repeat Binding Protein 2, Fmr1 protein, Mice, Knockout, messenger RNA, adult, nuclear export signal, presynaptic nerve, protein domain, RNA-Binding Proteins, unclassified drug, female, fragile X mental retardation protein, Female, protein RNA binding, 570, animal experiment, protein assembly, Enterobacteria phage MS2, Article, animal tissue, dendrite, hippocampal neuronal culture, telomeric repeat binding factor 2, mitochondrial membrane, Animals, Humans, controlled study, human, nerve fiber, RNA, Messenger, protein motif, TRF2 protein, protein expression, mouse, multigene family, nonhuman, binding site, neurology, human cell, 500, Biological Transport, nerve cell plasticity, brain cell, RNA binding protein, TRF2 S protein, Axons, Rats, Mice, Inbred C57BL, alpha tubulin, carrier protein, cell differentiation, neurotransmitter release, plasticity, RNA, protein, Carrier Proteins
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).34 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!