Unknown

Dataset Information

0

Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction.


ABSTRACT: 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.

PROVIDER: S-EPMC7269834 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC3812006 | BioStudies
| S-EPMC5126972 | BioStudies
| S-EPMC5800954 | BioStudies
| S-EPMC6976644 | BioStudies
| S-EPMC6000831 | BioStudies
2021-12-31 | GSE181706 | GEO
| S-EPMC6182776 | BioStudies
| S-EPMC6954203 | BioStudies
| PRJNA545193 | ENA
| S-EPMC8183684 | BioStudies