title: A-to-I RNA editing promotes developmental stage-specific gene and lncRNA expression.
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, mainly noncoding. Mutations in ADAR enzymes inCaenorhabditis eleganscause defects in normal development but are not lethal as in human and mouse. Previous studies inC. elegansindicated competition between RNA interference (RNAi) and RNA editing mechanisms, based on the observation that worms that lack both mechanisms do not exhibit defects, in contrast to the developmental defects observed 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 nonrepetitive 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 down-regulated 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. We found that many pseudogenes and other lncRNAs are also extensively down-regulated in the absence of ADARs in the embryo but not in the fourth larval (L4) stage. This down-regulation 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.
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Goldstein
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Lily
authors.initials: L
authors.lastname: Agranat-Tamir
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Dean
authors.initials: D
authors.lastname: Light
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Ben-Naim Zgayer
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Alla
authors.initials: A
authors.lastname: Fishman
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Ayelet T
authors.initials: AT
authors.lastname: Lamm
mesh_terms: D020413:3' Untranslated Regions; D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007288:Inosine / Q000378:metabolism; D009154:Mutation; D017393:RNA Editing; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D062085:RNA, Long Noncoding; D007288:Inosine; D000243:Adenosine Deaminase; D000241:Adenosine