RNAi screening for modulators of an osmo-sensitive gene response to extracellular matrix damage reveals negative feedback and interactions with translation inhibition

PLoS One. 2023 May 8;18(5):e0285328. doi: 10.1371/journal.pone.0285328. eCollection 2023.


In epidermal tissues, extracellular matrices (ECMs) function as barriers between the organism and environment. Despite being at the interface with the environment, little is known about the role of animal barrier ECMs in sensing stress and communicating with cytoprotective gene pathways in neighboring cells. We and others have identified a putative damage sensor in the C. elegans cuticle that regulates osmotic, detoxification, and innate immune response genes. This pathway is associated with circumferential collagen bands called annular furrows; mutation or loss of furrow collagens causes constitutive activation of osmotic, detoxification, and innate immune response genes. Here, we performed a genome-wide RNAi screen for modulators of osmotic stress response gene gpdh-1 in a furrow collagen mutant strain. RNAi of six genes identified in this screen were tested under other conditions and for effects on other stress responses. The functions of these genes suggest negative feedback within osmolyte accumulation pathways and interactions with ATP homeostasis and protein synthesis. Loss of these gpdh-1 modulators had distinct effects on canonical detoxification and innate immune response genes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • Collagen / metabolism
  • Extracellular Matrix / metabolism
  • Feedback
  • RNA Interference


  • Caenorhabditis elegans Proteins
  • Collagen

Associated data

  • figshare/10.6084/m9.figshare.21179404

Grants and funding

This study was supported by National Science Foundation grant IOS-1452948 to K.P.C; all authors received some salary from this funding source. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.