To investigate further, Schimmel collaborated with colleagues at TSRI in California and Florida, HKUST (including at the IAS), the San Diego biotech company aTyr Pharma (which Schimmel co-founded), Stanford and the Hong Kong biotech company Pangu Biopharma (an aTyr subsidiary).
Using advanced, sensitive techniques, the team identified nearly 250 previously unknown gene-transcript variants of AARS in different human cell types. These variants, known as splice variants, are alternative assemblies of the discrete sequences of information (exons) contained in AARS genes. Genes frequently contain multiple exons that can be spliced together in alternative waysthus in principle enabling a single active gene to encode multiple proteins with different functions. But the new findings suggest that evolution has been unusually prolific at creating AARS splice variants.
Potential New Class of Drug Targets
The team's further investigations revealed that the new AARS variants often are produced only in specific cell types such as brain or immune cells and/or appear only during certain stages of development.
Remarkably, most of the new splice variants lack entirely the standard "catalytic domain" that supports protein translationconfirming that they are not directly involved in that fundamental process. Initial screening of the biological activities of these variants hinted at a diversity of other functions. One variant selected for analysis turned out to be a powerful driver for the proliferation of muscle fiber cells in a laboratory di
|Contact: Mika Ono|
Scripps Research Institute