| Autor: |
Deffit SN; Medical Sciences Program, Indiana University, Bloomington, Indiana., Yee BA; Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States., Manning AC; Medical Sciences Program, Indiana University, Bloomington, Indiana., Rajendren S; Department of Biology, Indiana University, Bloomington, Indiana., Vadlamani P; Medical Sciences Program, Indiana University, Bloomington, Indiana., Wheeler EC; Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States., Domissy A; Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States., Washburn MC; Department of Biology, Indiana University, Bloomington, Indiana., Yeo GW; Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States.; Molecular Engineering Laboratory, Agency for Science, Technology and Research, Singapore, Singapore.; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Hundley HA; Medical Sciences Program, Indiana University, Bloomington, Indiana. |
| Abstrakt: |
ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans , we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans , on the neural transcriptome. Development and implementation of publicly available software, SAILOR, identified 7361 A-to-I editing events across the neural transcriptome. Intersecting the neural editome with adr-2 associated gene expression changes, revealed an edited mRNA, clec-41 , whose neural expression is dependent on deamination. Restoring clec-41 expression in adr-2 deficient neural cells rescued the chemotaxis defect, providing the first evidence that neuronal phenotypes of ADAR mutants can be caused by altered gene expression. |
