Coordinating gene expression using RNA destabilizing elements

A method of expressing a plurality of transgenes, comprising the steps of:

• obtaining a primary T-cell comprising a receptor, a first heterologous nucleic acid comprising a polynucleotide encoding a first transgene, and a polynucleotide encoding a first RNA destabilizing element (RDE), wherein the first RDE is an AU rich element, a second heterologous nucleic acid comprising a polynucleotide encoding a second transgene, and a polynucleotide encoding a second RDE, wherein the second RDE is an AU rich element, wherein the first heterologous nucleic acid is transcribed to make a first transcript encoding the first transgene operably linked to the first RDE, wherein a glycolytic enzyme with RDE binding activity-binds to the first RDE and regulates expression of the first transgene, and the second heterologous nucleic acid is transcribed to make a second transcript encoding the second transgene operably linked to the second RDE, wherein the glycolytic enzyme with RDE binding activity-binds to the second RDE and regulates expression of the second transgene;
• and binding the receptor on the primary T-cell to a ligand wherein binding of the ligand by the receptor activates the primary T-cell and the primary T-cell increases glycolytic activity whereby the glycolytic enzyme with RDE binding activity catalyzes a step of glycolysis, wherein activation of glycolysis in the primary T-cell reduces the amount of the glycolytic enzyme with RDE binding activity available to bind the first RDE and reduces the amount of the glycolytic enzyme with RDE binding activity available to bind the second RDE which produces increased expression of the first and second transgenes.