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

## TL;DR

This study shows how the protein Scd6 helps yeast cells respond to oxidative stress by controlling the production of an enzyme that fights harmful peroxides.

## Contribution

The study reveals a novel mechanism where Scd6 regulates CTT1 mRNA translation during oxidative stress by forming puncta.

## Key findings

- Scd6 forms stress-induced puncta that do not overlap with P-bodies or stress granules.
- Scd6 represses CTT1 mRNA translation, and its overexpression increases ROS and H2O2 sensitivity.
- Human LSm14A, the Scd6 homolog, also localizes to puncta and reduces survival under oxidative stress.

## Abstract

In response to stress, cells undergo gene expression reprogramming to cope with external stimuli. Cells utilize a conserved stress response mechanism called global downregulation of translation, leading to the storage of translationally repressed mRNAs in RNA granules. During oxidative stress induced by H2O2, genes responsible for combating oxidative stress, such as catalases, are strongly induced. However, the post-transcriptional regulatory events affecting these genes during H2O2 stress are not well-explored. Scd6, an RGG-motif-containing protein in yeast, acts as a translational repressor through its interaction with eIF4G1. This study identifies the role of Scd6 in oxidative stress response by regulating cytoplasmic catalase T1 (CTT1). We observe that peroxide stress induces the assembly of Scd6 puncta, which do not colocalize with P-bodies or stress granules. Scd6 overexpression increased sensitivity, while deletion enhanced tolerance to H2O2 treatment. Increased ROS accumulation and decreased Ctt1 protein levels were observed upon Scd6 overexpression due to translation repression of CTT1 mRNA. CTT1 mRNA interacts with Scd6. smFISH analysis and RNA immunoprecipitation studies reveal that localization of Scd6 to puncta upon peroxide stress reduces its interaction with CTT1 mRNA, allowing derepression. The role of Scd6 in peroxide stress response is conserved since the human homolog LSm14A also localizes to puncta upon H2O2 stress, and its overexpression reduces survival in response to peroxide stress. Overall, this study identifies a unique example of translation regulation whereby stress-induced localization of the translation repressor protein to puncta leads to derepression of the target mRNA.