Gene expression can be controlled at the post-transcriptional level through the 3’ untranslated region (3’ UTR) of mRNAs. 3’ UTRs are best known to be bound by regulatory proteins and miRNAs which often results in decreased protein expression by inhibiting translation or causing transcript degradation. However, 3’ UTRs act differently in the context of membrane proteins.
MSK investigators found that 3’UTRs are utilized by the majority of membrane proteins to achieve efficient surface expression. Many membrane proteins, especially those with several transmembrane domains, are hard to express on the cell surface in heterologous systems. MSK scientists determined that specific regulatory elements in 3’UTRs facilitate surface expression of membrane proteins. This invention describes a vector incorporating these 3’ UTR elements, which can be used as a tool for efficient expression of any protein on the cell surface.
- Broad applicability as a research tool to force expression of any protein to the cell surface
- Potential applications include cell surface expression of “hard to express” membrane proteins, including GPCRs in heterologous cells, and cell surface expression of receptors on the surface of immune cell including T cells
- Ready to use in a protein expression kit including a vector containing the elements responsible for surface localization; vector can be used to clone in any protein coding sequence
This technology could be developed into a protein expression kit to allow in vitro expression of any protein on the cell surface.
Provisional application 62/190,232 filed on July 8, 2015
Berkovits BD, Mayr C. Alternative 3’UTRs act as scaffolds to regulate membrane protein localization. Nature (2015). Epub 2015 Apr 20.
Christine Mayr, MD, PhD, Laboratory Head, Cancer Biology & Genetics Program, Memorial Sloan Kettering