PT  - JOURNAL ARTICLE
AU  - Hadi Tabarraei
AU  - Brandon M. Waddell
AU  - Kelly Raymond
AU  - Sydney M. Murray
AU  - Ying Wang
AU  - Keith P. Choe
AU  - Cheng-Wei Wu
TI  - CCR4-NOT subunit CCF-1/CNOT7 interacts with the PAL-1/CDX-1 transcription factor to regulate multiple stress responses in <em>Caenorhabditis elegans</em>
AID  - 10.1101/2022.06.13.495535
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.13.495535
4099  - http://biorxiv.org/content/early/2022/06/13/2022.06.13.495535.short
4100  - http://biorxiv.org/content/early/2022/06/13/2022.06.13.495535.full
AB  - CCR4-NOT is a versatile eukaryotic protein complex that controls multiple steps in gene expression regulation from synthesis to decay. In yeast, CCR4-NOT has been implicated in stress response regulation, though this function in other organisms remains unclear. In a genome-wide RNAi screen, we identified a subunit of the CCR4-NOT complex, ccf-1, as a requirement for the C. elegans transcriptional response to cadmium and acrylamide stress. Using whole-transcriptome RNA sequencing, we show that knockdown of ccf-1 attenuates the activation of a broad range of stress protective genes in response to cadmium and acrylamide, including those encoding heat shock proteins and glutathione s-transferases. Consistently, survival assays show that knockdown of ccf-1 decreases C. elegans stress resistance. A yeast-2-hybrid screen using a CCF-1 bait identified the homeobox transcription factor PAL-1 as a physical interactor. Knockdown of pal-1 inhibits the activation of ccf-1 dependent stress genes and reduces C. elegans stress resistance. Gene expression analysis reveals that knockdown of pal-1 down-regulates the mRNA levels of elt-2 and elt-3, which serves as the master transcriptional co-regulators of stress response in the C. elegans intestinal and epidermal tissues respectively. These results reveal a new role for CCR4-NOT in stress response regulation with PAL-1 through the transcriptional control of elt-2 and elt-3 in C. elegans.Competing Interest StatementThe authors have declared no competing interest.