MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation

• DOI: 10.1016/j.celrep.2021.108946
• Publication Date: 2021-04-06T15:40:12Z
• Authors: Vijay Swahari; Ayumi Nakamura; Emilie Hollville; Hume Stroud; Jeremy M. Simon; Travis S. Ptacek; Matthew V. Beck; Cornelius Flowers; Jiami Guo; Charlotte Plestant; Jie Liang; C. Lisa Kurtz; Matt Kanke; Scott M. Hammond; You-Wen He; E.S. Anton; Praveen Sethupathy; Sheryl S. Moy; Michael E. Greenberg; Mohanish Deshmukh
• Keywords: miR-29; Supplementary Data; QH301-705.5; General Biochemistry,Genetics and Molecular Biology; autism; 610; Down-Regulation; QH426 Genetics; Article; Cellular and Molecular Neuroscience; 03 medical and health sciences; Developmental Neuroscience; Seizures; 616; Animals; DNA (Cytosine-5-)-Methyltransferases; Biology (General); QH426; 3' Untranslated Regions; MeCP2; miRNA; seizures; Neurons; 0303 health sciences; Base Sequence; Behavior, Animal; neurodevelopmental disorders; 500; Brain; Gene Expression Regulation, Developmental; CH methylation; non-CG methylation; DNA Methylation; Up-Regulation; Mice, Inbred C57BL; MicroRNAs; Animals, Newborn; Neurodevelopmental Disorders; Synapses; RC0321; DNMT3A; epilepsy; RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry; Signal Transduction

Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal maturation are less understood. Here, we identify miR-29 family to be strikingly induced during late stages of maturation. Brain is associated with a transient, period de novo non-CG (CH) DNA methylation mediated by DNMT3A. We examine whether an important function restrict CH via its targeting Dnmt3a. Deletion in brain, or knockin mutations preventing specifically target Dnmt3a, result increased DNMT3A expression, higher methylation, repression genes neuronal activity neuropsychiatric disorders. These mouse models also develop neurological deficits premature lethality. Our results essential role for restricting illustrate importance regulation normal