A-to-I RNA editing promotes developmental stage–specific gene and lncRNA expression
| Autor: | Alla Fishman, Ayelet T. Lamm, Orna Ben-Naim Zgayer, Lily Agranat-Tamir, Boaz Goldstein, Dean Light |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Small interfering RNA Adenosine Adenosine Deaminase Pseudogene Biology 03 medical and health sciences 0302 clinical medicine RNA interference Gene expression Genetics Animals Caenorhabditis elegans Caenorhabditis elegans Proteins 3' Untranslated Regions Gene Genetics (clinical) Research Gene Expression Regulation Developmental RNA Inosine Cell biology 030104 developmental biology RNA editing Mutation ADAR RNA Long Noncoding RNA Editing 030217 neurology & neurosurgery |
| Zdroj: | Genome Research. 27:462-470 |
| ISSN: | 1549-5469 1088-9051 |
| DOI: | 10.1101/gr.211169.116 |
| Popis: | 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 in Caenorhabditis 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, 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. |
| Databáze: | OpenAIRE |
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