Host: Prof. Xin Jin, East China Normal University
Abstract
N6-Methyladenosine (m6A) RNA modification is a highly prevalent RNA modification in the mammalian brains. The RNA modification plays a crucial role in fundamental brain functions such as development, learning and memory, metabolism, circadian rhythm, injury-induced regeneration, and more. Despite its significance, the mechanisms by which m6A signals are transduced into neuronal and synaptic functions remain poorly understood. Previously, we have cataloged synaptically localized m6A-modified transcripts in synaptosomes, which included thousands of modified transcripts involved in neurodevelopmental and neuropsychiatric pathways. Potentially a large portion of the synaptic cleft proteome is encoded by the modified RNA species. To understand the decoding of m6A in dendrites and axons, we have focused on a cytoplasmic m6A reader YTH family proteins of which YTHDF3 is least characterized. We have generated transgenic mice models with specific deletion of YTHDF3 in mature excitatory neurons. Behavioral analysis of the YTHDF3-deficient mice suggests deviations in behavioral patterns including adaptive stress-coping, motivation, and repetitive-visits behaviors in the animals. Using high-throughput fluorescence imaging methods, we performed morphometric analysis on thousands of spines in each animal's brain and observed massive alterations representing disorganization. Our study supports the functional relevance of m6A signals to local spine development and circuit connectivity through excitatory synaptic transmission.
Biography
Dr. Dan Ohtan Wang is a molecular and cellular neuroscientist to study how gene expression in neurons is connected to the environment and experience. Her lab focus on the post-transcriptional regulation mechanisms such as RNA trafficking and dynamic epitranscriptomic regulation (RNA epigenetics). She completed a BA in Bioengineering at Tokyo Institute of Technology in Japan, a PhD in Neurosciences at the University of Southern California in the USA (2004), and postdoctoral training in The UCLA Department of Psychiatry and Biobehavioral Sciences (2010).
She started her lab as an assistant professor at Kyoto University in 2012. She pioneered RNA live-imaging techniques using hybridization-sensitive fluorescent probes and succeeded in ex vivo RNA imaging in living brain tissues. Her lab also reported the first draft of synaptically localized messenger RNAs with N6-methyl-adenosine modifications in 2018. The initial findings have suggested functional links to the synaptic organization and neuropsychiatric diseases, but the underlying cellular pathways and molecular platforms remain to be revealed. She will be setting up a neuroepitrancriptomics lab at NYUAD to study* how versatile RNA modifications modulate gene expression in space and time responsible for behavioral adaptation.