Phosphorylation Of MSI-1 Is Required For Forgetting In Caenorhabditis Elegans

The Musashi family of RNA-binding proteins controls several biological processes including stem cell maintenance, cell division, and neural function. Previously, we demonstrated that the C. elegans Musashi ortholog, msi-1, regulates forgetting via translational repression of the Arp2/3 actin-branching complex. However, the mechanisms controlling MSI-1 activity during the regulation of forgetting are currently unknown. Here we investigated the effects of post-translational modifications on MSI-1 activity. We show that MSI-1 function is likely controlled by alterations of its activity rather than its expression levels. Furthermore, we found that MSI-1 is phosphorylated and identified the phosphorylation sites in the worm MSI-1 using mass spectrometry. Moreover, CRISPR-based manipulations of MSI-1 phosphorylation sites revealed that phosphorylation is necessary for MSI-1 function in both short- and long-term memory. Thus, our study provides a first insight into the controlling mechanism of MSI-1 activity during forgetting and may facilitate the development of novel therapeutic approaches.