Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
17
05
2019
accepted:
19
03
2020
pubmed:
6
5
2020
medline:
15
9
2020
entrez:
6
5
2020
Statut:
ppublish
Résumé
DNA forms conformational states beyond the right-handed double helix; however, the functional relevance of these noncanonical structures in the brain remains unknown. Here we show that, in the prefrontal cortex of mice, the formation of one such structure, Z-DNA, is involved in the regulation of extinction memory. Z-DNA is formed during fear learning and reduced during extinction learning, which is mediated, in part, by a direct interaction between Z-DNA and the RNA-editing enzyme Adar1. Adar1 binds to Z-DNA during fear extinction learning, which leads to a reduction in Z-DNA at sites where Adar1 is recruited. Knockdown of Adar1 leads to an inability to modify a previously acquired fear memory and blocks activity-dependent changes in DNA structure and RNA state-effects that are fully rescued by the introduction of full-length Adar1. These findings suggest a new mechanism of learning-induced gene regulation that is dependent on proteins that recognize alternate DNA structure states, which are required for memory flexibility.
Identifiants
pubmed: 32367065
doi: 10.1038/s41593-020-0627-5
pii: 10.1038/s41593-020-0627-5
pmc: PMC7269834
mid: NIHMS1578355
doi:
Substances chimiques
DNA, Z-Form
0
RNA, Small Interfering
0
ADAR1 protein, mouse
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
718-729Subventions
Organisme : NIMH NIH HHS
ID : R01 MH105398
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109588
Pays : United States
Commentaires et corrections
Type : ErratumIn
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