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Ribosome profiling reveals post-translational signaling mechanisms drive the retrograde enhancement of presynaptic efficacy

By Xun Chen, Dion Dickman

Posted 30 Jun 2017
bioRxiv DOI: 10.1101/158303 (published DOI: 10.1371/journal.pgen.1007117)

Presynaptic efficacy can be modulated by retrograde control mechanisms, but the nature of these complex signaling systems remain obscure. We have developed and optimized a tissue-specific ribosome profiling approach in Drosophila. We first demonstrate the ability of this technology to define genome-wide translational regulations. We then leverage this technology to test the relative contributions of transcriptional, translational, and post-translational mechanisms in the postsynaptic muscle that orchestrate the retrograde control of presynaptic function. Surprisingly, we find no changes in transcription or translation are necessary to enable retrograde homeostatic signaling. Rather, post-translational mechanisms appear to ultimately gate instructive retrograde communication. Finally, we find that a global increase in translation induces adaptive responses in both transcription and translation of protein chaperones and degradation factors to promote cellular proteostasis. Together, this demonstrates the power of ribosome profiling to define transcriptional, translational, and post-translational mechanisms driving retrograde signaling during adaptive plasticity.

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