Profiling neural editomes reveals a molecular mechanism to regulate RNA editing during development
| Autor: | Suba Rajendren, Alfa Dhakal, Jack Townsend, Sarah N. Deffit, Pranathi Vadlamani, Heather A. Hundley |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adenosine
Adenosine Deaminase Cell Biology 03 medical and health sciences 0302 clinical medicine Gene expression Genetics medicine Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Psychological repression Gene Genetics (clinical) 030304 developmental biology 0303 health sciences Research RNA Inosine Cell biology medicine.anatomical_structure RNA editing ADAR RNA Editing Neural development 030217 neurology & neurosurgery |
| Zdroj: | Genome Res |
| Popis: | Adenosine (A) to inosine (I) RNA editing contributes to transcript diversity and modulates gene expression in a dynamic, cell type–specific manner. During mammalian brain development, editing of specific adenosines increases, whereas the expression of A-to-I editing enzymes remains unchanged, suggesting molecular mechanisms that mediate spatiotemporal regulation of RNA editing exist. Herein, by using a combination of biochemical and genomic approaches, we uncover a molecular mechanism that regulates RNA editing in a neural- and development-specific manner. Comparing editomes during development led to the identification of neural transcripts that were edited only in one life stage. The stage-specific editing is largely regulated by differential gene expression during neural development. Proper expression of nearly one-third of the neurodevelopmentally regulated genes is dependent on adr-2, the sole A-to-I editing enzyme in C. elegans. However, we also identified a subset of neural transcripts that are edited and expressed throughout development. Despite a neural-specific down-regulation of adr-2 during development, the majority of these sites show increased editing in adult neural cells. Biochemical data suggest that ADR-1, a deaminase-deficient member of the adenosine deaminase acting on RNA (ADAR) family, is competing with ADR-2 for binding to specific transcripts early in development. Our data suggest a model in which during neural development, ADR-2 levels overcome ADR-1 repression, resulting in increased ADR-2 binding and editing of specific transcripts. Together, our findings reveal tissue- and development-specific regulation of RNA editing and identify a molecular mechanism that regulates ADAR substrate recognition and editing efficiency. |
| Databáze: | OpenAIRE |
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