RGG-motif protein Scd6 affects oxidative stress response by regulating Cytosolic caTalase T1 (Ctt1)

Abstract

In response to stress, cells undergo gene expression reprogramming to cope with external stimuli. As translation is energy consuming process, its regulation during stress is crucial for cellular adaptation. Cells utilize a conserved stress response mechanism called global downregulation of translation, leading to the storage of translationally repressed mRNAs in RNA granules or RNP condensates. During oxidative stress induced by H2O2, genes responsible for combating oxidative stress, such as catalases and glutathione peroxidase, are strongly induced. However, the post-transcriptional regulatory events affecting these genes during H2O2 stress are not well-explored. RNA binding proteins such as RGG motif proteins play a critical role in mediating translation regulation and have diverse physiological functions. Scd6, an RGG motif-containing protein in yeast, acts as a translational repressor through its interaction with eIF4G. Although the role of Scd6 as a translational repressor and decapping activator is known, its specific mRNA targets are largely unknown.This study identifies the role of Scd6 in oxidative stress response by regulating cytoplasmic catalaseT1 (CTT1). Altering Scd6 levels influenced Ctt1 protein levels, thereby affecting oxidative stress response. Scd6 overexpression increased sensitivity, while deletion enhanced tolerance to H2O2 treatment due to ROS accumulation in the yeast cell. In response to H2O2 treatment, Scd6 forms dynamic puncta which contains RNA. Overall, this study proposes regulation of oxidative stress response via modulation of CTT1 mRNA by Scd6.