Expression of a cloned human interleukin-2 cDNA is enhanced by the substitution of a heterologous mRNA leader region.

A cloned interleukin-2 (IL-2) cDNA was poorly expressed in transfected eukaryotic cells. This low expression was only partly relieved by removal of the homopolymer tail present in the 5' leader region of the encoded IL-2 mRNA. However, replacement of the natural IL-2 mRNA 5' noncoding region with a leader element derived from the efficiently translated rat preproinsulin II mRNA resulted in an mRNA molecule that was utilized effectively by the transfected cell. The enhanced expression of this chimeric IL-2 mRNA did not appear to be due to changes in the sequence near the translation initiation codon. These results suggest that the leader elements of efficiently translated mRNAs may be able to confer a higher translational efficiency on heterologous protein coding regions when present in cis.