A-to-I RNA editing promotes developmental-stage-specific gene and lncRNA expression
- Boaz Goldstein,
- Lily Agranat-Tamir,
- Dean Light,
- Orna Ben-Naim Zgayer,
- Alla Fishman and
- Ayelet T Lamm1
- ↵* Corresponding author; email: ayeletla{at}tx.technion.ac.il
Abstract
A-to-I RNA editing is a conserved widespread phenomenon in which adenosine (A) is converted to inosine (I) by adenosine deaminases (ADARs) in double-stranded RNA regions. Although human RNAs contain millions of A-to-I editing sites, most of these occur in noncoding regions and their function is unknown. Mutations in ADAR enzymes in C. elegans cause defects in normal development but are not lethal as in human and mouse. Previous studies in C. elegans indicated competition between RNA interference (RNAi) and RNA editing mechanisms, with the observation that worms that lack both mechanisms do not exhibit defects when only RNA editing is absent. To study the effects of RNA editing on gene expression and function we established a novel screen that enabled us to identify thousands of RNA editing sites in non-repetitive regions in the genome. These include dozens of genes that are edited at their 3'UTR region. We found that these genes are mainly germline and neuronal genes, and that they are downregulated in the absence of ADAR enzymes. Moreover, we discovered that almost half of these genes are edited in a developmental-specific manner, indicating that RNA editing is a highly regulated process. In addition, we found that many pseudogenes and other lncRNAs are also extensively downregulated in the absence of ADARs in embryo but not in L4 larva developmental stage. This downregulation is not observed upon additional knockout of RNAi. Furthermore, levels of siRNAs aligned to pseudogenes in ADAR mutants are enhanced. Taken together, our results suggest a role for RNA editing in normal growth and development by regulating silencing via RNAi.
- Received June 13, 2016.
- Accepted December 20, 2016.
- Published by Cold Spring Harbor Laboratory Press
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