Drosophila and human Headcase define a new family of ribonucleotide granule proteins required for stress response.

Cells have means to adapt to environmental stresses such as temperature fluctuations, toxins, or nutrient availability. Stress responses, being dynamic, extend beyond transcriptional control and encompass post-transcriptional mechanisms allowing for rapid changes in protein synthesis. Previous research has established headcase as a fundamental gene for stress responses and survival of the Drosophila adult progenitor cells (APCs). However, the molecular role of Headcase has remained elusive. Here, we identify Headcase as a component of ribonucleoprotein (RNP) granules. We also show that, Headcase is required for proper RNP granule formation and remodeling upon stress and is crucial for translation control. Likewise, the human Headcase homolog (HECA) is identified as a component of RNP granules and has similar roles in translational regulation and stress protection. Thus, Headcase proteins define a new family contributing to specific roles among the RNP heterogeneous network.