Translocation of cytosolic hCdc73 to stress granules plays a role in arsenic stress-induced stabilization of p53 mRNA.

Abstract

Cells trigger the assembly of stress granules (SGs) under various stress conditions. Among the many proteins recruited to SGs are RNA-binding proteins and transcription regulators. Here, we report the translocation of hCdc73, a component of the PAF1 transcription complex, to cytosolic SGs in response to arsenic stress. The hCdc73 protein possesses a long intrinsically disordered region (IDR) from amino acids 256-416, the presence of which is required for the translocation of hCdc73 to cytosolic SGs. The purified hCdc73 IDR formed droplets in vitro, and the light-activated assembly of hCdc73 IDR-mCherry-CRY2 was verified. For translocation of hCdc73 to SGs, physical interactions with the carrier proteins of SGs, such as FMR1, are also needed. Previously, we reported that the cytosolic hCdc73/eEF1Bγ complex controls the stability of p53 mRNA. Under arsenic stress, selective sequestration of cytosolic hCdc73, but not eEF1Bγ or p53 mRNA, was detected. As a result, a transient increase in p53 mRNA at the posttranscriptional level was observed. In conclusion, we propose that the availability of mRNAs for stress-responsive genes can be controlled by restraining their negative regulators within SGs.