Title: Amorphous SiO2 nanoparticles promote cardiac dysfunction via the opening of the mitochondrial permeability transition pore in rat heart and human cardiomyocytes
Authors: Lozano, O
Silva-Platas, C
Chapoy-Villanueva, H
Perez, BE
Lees, JG
Ramachandra, CJA
Contreras-Torres, FF
Lazaro-Alfaro, A
Luna-Figueroa, E
Bernal-Ramirez, J
Gordillo-Galeano, A
Benitez, A
Oropeza-Almazan, Y
Castillo, EC
Koh, PL
Hausenloy, DJ
Lim, SY
Garcia-Rivas, G
Issue Year: 2020
Publisher BMC
Abstract Marshall et al. show that regions of the genome adopt a noncanonical Z-DNA state in the prefrontal cortex in response to fear learning and that binding of Adar1 reduces Z-DNA during extinction learning, which is required for memory flexibility. 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.
URI: https://publications.svi.edu.au/publications/7206
Other Identifiers 10.1186/s12989-020-00346-2
Publication type Article