ADARs regulate cuticle collagen expression and promote survival to pathogen infection

Alfa Dhakal, Chinnu Salim, Mary Skelly, Yarden Amichan, Ayelet T. Lamm, Heather A. Hundley

Research output: Contribution to journalArticlepeer-review


Background: In all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that act on RNA (ADAR) family of RNA-binding proteins has been reported to influence innate immunity in metazoans. However, studies on the susceptibility of ADAR mutant animals to infection are largely lacking. Results: Here, by analyzing adr-1 and adr-2 null mutants in well-established slow-killing assays, we find that both Caenorhabditis elegans ADARs are important for organismal survival to gram-negative and gram-positive bacteria, all of which are pathogenic to humans. Furthermore, our high-throughput sequencing and genetic analysis reveal that ADR-1 and ADR-2 function in the same pathway to regulate collagen expression. Consistent with this finding, our scanning electron microscopy studies indicate adr-1;adr-2 mutant animals also have altered cuticle morphology prior to pathogen exposure. Conclusions: Our data uncover a critical role of the C. elegans ADAR family of RNA-binding proteins in promoting cuticular collagen expression, which represents a new post-transcriptional regulatory node that influences the extracellular matrix. In addition, we provide the first evidence that ADAR mutant animals have altered susceptibility to infection with several opportunistic human pathogens, suggesting a broader role of ADARs in altering physical barriers to infection to influence innate immunity.

Original languageEnglish
Article number37
Pages (from-to)37
JournalBMC Biology
Issue number1
StatePublished - 16 Feb 2024


  • C. elegans
  • Double-stranded RNA (dsRNA)
  • Innate immunity
  • P. aeruginosa
  • Post-transcriptional regulation
  • RNA editing
  • RNA modification
  • RNA-binding protein
  • RNA Editing
  • Humans
  • RNA-Binding Proteins/genetics
  • Animals
  • Caenorhabditis elegans/genetics
  • Collagen/genetics
  • Adenosine Deaminase/genetics
  • Caenorhabditis elegans Proteins/genetics

ASJC Scopus subject areas

  • Biotechnology
  • Structural Biology
  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • Plant Science
  • Developmental Biology
  • Cell Biology


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