Seminar Series - Haissi Cui

Title: Aminoacyl-tRNA synthetases in mRNA translation and beyond

Abstract:

Shared among all life forms is that genetic information is stored as DNA, which is transcribed into mRNA and translated into proteins. During this process, aminoacyl-tRNA synthetases catalyze the first step of protein synthesis by physically linking the building blocks of proteins, amino acids, to transfer-RNA (tRNA) adapters. These “charged” tRNAs are then used by the ribosome to assemble the linked amino acids into proteins according to the information provided by mRNA. Philosophically, tRNA aminoacylation can therefore be seen as the moment during which the genetic code is interpreted, as nucleotide triplets are assigned to amino acids.

Recently, we have come to appreciate that RNA processes in mammalian cells can be highly localized. However, we still do not know where aminoacylation takes place in mammalian cells and which principles govern the trafficking of aminoacyl-tRNA synthetases, partially because we lack appropriate methods to study this process. My group aims to develop and use chemical tools, genome engineering, and relevant disease models to visualize aminoacylation, manipulate RNA and protein localization within mammalian cells, and study the consequences of mutations that cause human diseases. Building on previous work, which suggests the control of aminoacyl-tRNA synthetase localization as an evolutionary drive and a regulator of both translational and moonlighting functions, we use a mix of chemistry, biochemistry, cell biology, and animal models to study RNA processes from molecule to mouse.