C. elegans ADARs antagonize silencing of cellular dsRNAs by the antiviral RNAi pathway

  1. Brenda L. Bass
  1. Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112, USA
  1. Corresponding author: bbass{at}biochem.utah.edu
  • 1 Present address: Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

Abstract

Cellular dsRNAs are edited by adenosine deaminases that act on RNA (ADARs). While editing can alter mRNA-coding potential, most editing occurs in noncoding sequences, the function of which is poorly understood. Using dsRNA immunoprecipitation (dsRIP) and RNA sequencing (RNA-seq), we identified 1523 regions of clustered A-to-I editing, termed editing-enriched regions (EERs), in four stages of Caenorhabditis elegans development, often with highest expression in embryos. Analyses of small RNA-seq data revealed 22- to 23-nucleotide (nt) siRNAs, reminiscent of viral siRNAs, that mapped to EERs and were abundant in adr-1;adr-2 mutant animals. Consistent with roles for these siRNAs in silencing, EER-associated genes (EAGs) were down-regulated in adr-1;adr-2 embryos, and this was dependent on associated EERs and the RNAi factor RDE-4. We observed that ADARs genetically interact with the 26G endogenous siRNA (endo-siRNA) pathway, which likely competes for RNAi components; deletion of factors required for this pathway (rrf-3 or ergo-1) in adr-1;adr-2 mutant strains caused a synthetic phenotype that was rescued by deleting antiviral RNAi factors. Poly(A)+ RNA-seq revealed EAG down-regulation and antiviral gene induction in adr-1;adr-2;rrf-3 embryos, and these expression changes were dependent on rde-1 and rde-4. Our data suggest that ADARs restrict antiviral silencing of cellular dsRNAs.

Keywords

Footnotes

  • Received December 19, 2017.
  • Accepted January 26, 2018.

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