RESEARCH

“Epitranscriptomics” is a relatively new field that spans several disciplines to identify the molecular mechanisms and functional significance of chemical modifications on RNA. The discovery of RNA methyltransferases, demethylases, and modified-RNA binding proteins (“readers”) has transformed our understanding of how RNA processing in the cell regulates a myriad of processes, from neural development to cancer biology.

An important aspect of the epitranscriptome is that it is dynamic in nature- which gene transcripts are modified and the downstream effects of modification changes over developmental time, cell type, and in response to stimuli. The Vissers Lab is particularly interested in understanding the regulation of the epitranscriptome- what prompts dynamic changes in the system that in turn regulate the way a cell responds to internal or external stimuli? Can these pathways be manipulated to alter cell behavior in development and disease?

Interconnectivity of the epitranscriptome: there are many possible modifications that can occur on RNA, especially methylations at numerous distinct positions in mRNA, tRNA, and rRNA. Some of the well-characterized modifications include m6A, m1A, m6Am, and m5C. Preliminary data show that there may be interconnectivity between the regulation of multiple modifications, adding a new layer of complexity to our understanding of the epitranscriptome.

Applications in neuroscience: mRNA is most highly methylated in the brain, and Dr. Vissers’ previous work detailed the critical role of m6A mRNA methylation in the developing brain and helped identify the role of m6A in neuro-developmental disorders like Fragile X Syndrome. Others have shown that m6A also regulates learning and memory in the adult brain. We are interested in further investigating the role of m6A in normal and disordered brain development by taking an evolutionary approach supplemented with the use of human brain organoids and stem cell culture.