Alternative mRNA Translation and Cell Type-Specific Proteoforms in the Brain

2025 Seed Grant
Junjie Guo, Ph.D.
Yale University

Although all cells in the brain share the same DNA, they differ greatly in shape and function. This diversity may partly arise from how individual mRNAs are translated into proteins, through a process known as alternative mRNA translation. The Guo lab has found that protein synthesis on some mRNAs begin at multiple sites, producing similar yet distinct forms of protein (proteoforms) that influence the communication between nerve cells. In this new project, the team will develop cutting-edge tools to globally identify mRNA translation start sites in different cell types in the brain to understand how alternative mRNA translation may shape each cell type’s unique identity and function, offering new insights into brain development, circuitry, and disease. Relevant neurological diseases: Amyotrophic lateral sclerosis, frontotemporal dementia, fragile X syndrome
 

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