Translation control of autophagy genes upon hydroxyurea-induced genotoxic stress

The fine balance between cellular homeostasis and stress response is crucial for cell survival. In this study, we identify translation regulation of specific autophagy (ATGs) genes by translation repressor Sbp1 upon hydroxyurea-mediated genotoxic stress. Sbp1 localizes to reversible, mRNA-containing granules specifically upon HU stress in RNA recognition motif 1 (RRM1) and RGG motif-dependent manner. Granule localization is independent of eIF4G1 binding despite increased arginine methylation. Deletion of SBP1 increased the tolerance to HU. RNA sequencing of polysome fractions identified ATG1, 2, 9 mRNAs being translationally upregulated in Δsbp1 upon HU stress. Translation of TEL1 and MEC1, the upstream activators of autophagy, also increased in Δsbp1. Concomitantly, increased autophagy and decreased NHEJ repair in Δsbp1 cells was observed. Together, these findings identify Sbp1 as a regulator of the autophagy pathway in response to genotoxic stress by modulating autophagy at two levels, possibly mediated by its ability to localize to granules.