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

Abstract

Titlow et al. find that Syncrip (hnRNPQ RNA binding protein) acts directly on msp300 to modulate activity-dependent synaptic plasticity. In vivo biophysical experiments reveal activity-dependent changes in RNP complex sizes compatible with an increase in translation at the synapse. AbstractMemory and learning involve activity-driven expression of proteins and cytoskeletal reorganisation at new synapses, often requiring post-transcriptional regulation a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organises actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is not yet known. Here, we show that the local translation of msp300 is promoted during activity-dependent plasticity by the conserved RNA binding protein Syncrip/hnRNP Q, which binds to msp300 transcripts and is essential for plasticity. Single molecule imaging shows that Syncrip is associated in vivo with msp300 mRNA in ribosome-rich particles. Elevated neural activity alters the dynamics of Syncrip RNP granules at the synapse, suggesting a change in particle composition or binding that facilitates translation. These results introduce Syncrip as an important early-acting activitydependent translational regulator of a plasticity gene that is strongly associated with human ataxias.

A cell-type-specific multi-protein complex regulates expression of Cyclin B protein inDrosophilamale meiotic prophase

“…In the larval neuromuscular junction, Syp acts post-synaptically to block synaptic overgrowth, binding multiple target RNAs (McDermott et al 2014). Syp binds the MSP-300 RNA, co-localizes with it in vivo to ribosome-dense granules (Titlow et al, 2020), and promotes translation of MSP-300 in a neural-activity dependent manner. In the Drosophila mushroom body, Syp and another RNA-binding protein Imp appear in opposing temporal gradients and regulate cell fate decisions (g, a'/b', or a/b neurons), with Syp antagonizing and Imp promoting expression of Chinmo protein without either factor affecting chinmo RNA abundance (Liu et al, 2015).…”

“…10B) presents the possibility that Syp could be factor Y, suppressing Rbp4 function in maturing spermatocytes, while still acting in parallel with Rbp4 to stabilize the cycB RNA. In this model, Syp is present in mid-stage spermatocytes but not capable co-localizes with it in vivo to ribosome-dense granules (Titlow et al, 2020), and promotes translation of MSP-300 in a neural-activity dependent manner. In the Drosophila mushroom body, Syp and another RNA-binding protein Imp appear in opposing temporal gradients and regulate cell fate decisions (g, a'/b', or a/b neurons), with Syp antagonizing and Imp promoting expression of Chinmo protein without either factor affecting chinmo RNA abundance (Liu et al, 2015).…”