Syncrip/hnRNP Q is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation

Abstract

Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganization at new synapses, requiring posttranscriptional regulation of localized mRNA a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organizes actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is poorly understood. Here, we show that activity-dependent accumulation of Msp300 in the postsynaptic compartment of the Drosophila larval neuromuscular junction is regulated by the conserved RNA binding protein Syncrip/hnRNP Q. Syncrip (Syp) binds to msp300 transcripts and is essential for plasticity. Single-molecule imaging shows that msp300 is associated with Syp in vivo and forms ribosome-rich granules that contain the translation factor eIF4E. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these particles facilitate translation. These results introduce Syp as an important early acting activity-dependent regulator of a plasticity gene that is strongly associated with human ataxias.

RNA-binding protein syncrip regulates starvation-induced hyperactivity in adult Drosophila

“…The present finding is the first indication that Syp has a unique function in adult flies ( Fig 3 ) independent of its developmental effects ( Fig 4 ). At the subcellular and molecular level, previous studies have shown that Syp, in muscle cells at the Drosophila larval neuromuscular junction, can modulate the presynaptic vesicle release through regulating postsynaptic translation of a retrograde signal [ 30 ] and can regulate activity-dependent synaptic plasticity [ 58 ]. Similar functions have also been observed in mammalian SYNCRIP such that it is a component of neuronal RNA transport granules that can regulate dendritic morphology [ 48 , 59 – 61 ], and that it inhibits translation by competing with the poly(A) binding protein [ 62 ].…”

RNA-binding protein Syncrip regulates Starvation-Induced Hyperactivity in adultDrosophila

“…At the subcellular and molecular level, previous studies have shown that Syp, in muscle cells at the Drosophila larval neuromuscular junction, can modulate the presynaptic vesicle release through regulating postsynaptic translation of a retrograde signal [30] and can regulate activity-dependent synaptic plasticity [58]. Similar functions have also been observed in mammalian SYNCRIP such that it is a component of neuronal RNA transport granules that can regulate dendritic morphology [48,[59][60][61], and that it inhibits translation by competing with the poly(A) binding protein [62].…”

The role of hnRNPs in frontotemporal dementia and amyotrophic lateral sclerosis

“…Different hnRNP Q isoforms have been associated with differential splicing activity of the SMN2 exon 7 in the neurodegenerative disease SMA [ 144 ]. Further functions of hnRNP Q include the post-transcriptional modulation of circadian clock gene mRNAs levels [ 94 , 95 ], morphological development of neuromuscular junctions [ 194 ] and the exosomal sorting of specific micro RNAs [ 72 ]. Both hnRNP R and Q have been identified as potentially important regulators of neuronal homeostasis and cellular pathways associated with neurodegeneration [ 23 ].…”