@article{Rajendren01012021,
author = {Rajendren, Suba and Dhakal, Alfa and Vadlamani, Pranathi and Townsend, Jack and Deffit, Sarah N. and Hundley, Heather A.}, 
title = {Profiling neural editomes reveals a molecular mechanism to regulate RNA editing during development},
volume = {31}, 
number = {1}, 
pages = {27-39}, 
year = {2021}, 
doi = {10.1101/gr.267575.120}, 
abstract ={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.}, 
URL = {http://genome.cshlp.org/content/31/1/27.abstract}, 
eprint = {http://genome.cshlp.org/content/31/1/27.full.pdf+html}, 
journal = {Genome Research} 
}