In:
Genome Research, Cold Spring Harbor Laboratory, Vol. 31, No. 1 ( 2021-01), p. 27-39
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.
Type of Medium:
Online Resource
ISSN:
1088-9051
,
1549-5469
DOI:
10.1101/gr.267575.120
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2021
detail.hit.zdb_id:
1483456-X
SSG:
12
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