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CCR4-NOT subunit CCF-1/CNOT7 promotes transcriptional activation to multiple stress responses in Caenorhabditis

Hadi Tabarraei1, Brandon M Waddell1, Kelly Raymond1

  • 1Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Aging Cell
|February 16, 2023
PubMed

Insights

The CCR4-NOT complex subunit ccf-1 is crucial for C. elegans to respond to environmental toxins, regulating stress-protective genes and impacting lifespan. Its interaction with PAL-1 highlights a new role in stress resistance.

Area of Science:

  • Molecular Biology
  • Genetics
  • Environmental Science

Background:

  • The CCR4-NOT complex regulates gene expression in eukaryotes.
  • Its role in environmental stress response is not well understood in many organisms.
  • Previous studies linked CCR4-NOT to stress response in yeast.

Purpose of the Study:

  • To investigate the role of the CCR4-NOT complex in environmental stress response in C. elegans.
  • To identify specific subunits and interacting partners involved in this process.
  • To elucidate the molecular mechanisms underlying stress resistance and lifespan regulation by CCR4-NOT.

Main Methods:

  • Genome-wide RNAi screen to identify key genes.
  • Whole-transcriptome RNA sequencing to analyze gene expression changes.
  • Yeast two-hybrid screening to identify protein interactions.
  • Survival assays to assess stress resistance and lifespan.

Main Results:

  • Knockdown of ccf-1 (a CCR4-NOT subunit) impaired the transcriptional response to cadmium and acrylamide stress.
  • ccf-1 knockdown reduced the expression of stress-protective genes and decreased C. elegans survival and lifespan.
  • The homeobox transcription factor PAL-1 was identified as a CCF-1 interactor, and its knockdown also reduced stress resistance.
  • Both ccf-1 and pal-1 knockdown attenuated the activation of elt-2 and elt-3, key stress response regulators.

Conclusions:

  • The CCR4-NOT complex plays a significant role in the environmental stress response in C. elegans.
  • ccf-1 and its interactor PAL-1 are critical for activating stress-protective genes and maintaining stress resistance and longevity.
  • This study reveals a novel function for CCR4-NOT in mediating organismal defense against environmental toxins.
Keywords:
C. elegansaginglongevityoxidative stressstress response

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