Charles E. Kaufman Foundation

2022 New Initiative Grant

Andrea Berman, Ph.D. (PI)

Judith Yanowitz, Ph.D. (Co-PI)

Translation regulation of TMG-capped mRNAs – an evolutionary remnant of trans-splicing?


Abstract

Cell types are defined by the genes they express. For example, muscle cells express genes important for generating energy for muscle contraction. At the molecular level, a cell uses genetic information to selectively make proteins that perform the essential characteristic processes of each cell. While the core machinery that synthesizes proteins is universal, the way cells control which proteins are made has evolved. The major signals that direct protein synthesis in simple organisms, such as worms and disease-causing parasites, control a diminishing percentage of synthesis in complex animals. In humans, this small percentage is responsible for protecting cells from molecular stress caused by pollutants, inflammation and infection. Notably, some viruses hijack this mechanism to promote their conquest of the cell. The goal of this project is to identify the key molecules that worms and humans use to determine what proteins are made in specific cells, and then dissect how these proteins exert control at the molecular level. This research will reveal novel information about the evolution of this mechanism over hundreds of millions of years and could identify new treatment directions for parasitic infections and diseases afflicting humans, pets and livestock.

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