The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/28625 |
| _version_ | 1811236792638111744 |
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| author | Sarah N Deffit Brian A Yee Aidan C Manning Suba Rajendren Pranathi Vadlamani Emily C Wheeler Alain Domissy Michael C Washburn Gene W Yeo Heather A Hundley |
| author_facet | Sarah N Deffit Brian A Yee Aidan C Manning Suba Rajendren Pranathi Vadlamani Emily C Wheeler Alain Domissy Michael C Washburn Gene W Yeo Heather A Hundley |
| author_sort | Sarah N Deffit |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:15:16Z |
| format | Article |
| id | doaj.art-0be709163d094d89ae3e71f8c13c24d9 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:15:16Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0be709163d094d89ae3e71f8c13c24d92022-12-22T03:33:27ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.28625The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxisSarah N Deffit0Brian A Yee1Aidan C Manning2Suba Rajendren3Pranathi Vadlamani4Emily C Wheeler5Alain Domissy6Michael C Washburn7Gene W Yeo8Heather A Hundley9https://orcid.org/0000-0002-9106-9016Medical Sciences Program, Indiana University, Bloomington, IndianaDepartment of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United StatesMedical Sciences Program, Indiana University, Bloomington, IndianaDepartment of Biology, Indiana University, Bloomington, IndianaMedical Sciences Program, Indiana University, Bloomington, IndianaDepartment of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United StatesDepartment of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United StatesDepartment of Biology, Indiana University, Bloomington, IndianaDepartment 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, SingaporeMedical Sciences Program, Indiana University, Bloomington, IndianaADAR 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.https://elifesciences.org/articles/28625RNA editingADARgene expressionRNA biologypost-transcriptional gene regulationinosine |
| spellingShingle | Sarah N Deffit Brian A Yee Aidan C Manning Suba Rajendren Pranathi Vadlamani Emily C Wheeler Alain Domissy Michael C Washburn Gene W Yeo Heather A Hundley The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis eLife RNA editing ADAR gene expression RNA biology post-transcriptional gene regulation inosine |
| title | The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis |
| title_full | The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis |
| title_fullStr | The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis |
| title_full_unstemmed | The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis |
| title_short | The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis |
| title_sort | c elegans neural editome reveals an adar target mrna required for proper chemotaxis |
| topic | RNA editing ADAR gene expression RNA biology post-transcriptional gene regulation inosine |
| url | https://elifesciences.org/articles/28625 |
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