Few promoters are active at high levels in all cells. Of these, the majority encode structural RNAs transcribed by
RNA polymerases I or III and are not accessible for the expression of
proteins. An exception are the small nuclear RNAs (snRNAs) transcribed by
RNA polymerase II. Although
snRNA biosynthesis is unique and thought not to be compatible with synthesis of functional
mRNA, we have tested these promoters for their ability to express functional mRNAs. We have used the murine U1a and U1b
snRNA gene promoters to express the Escherichia coli lacZ gene and the human
alpha-globin gene from either episomal or integrated templates by transfection, or
infection into a variety of mammalian cell types. Equivalent expression of
beta-galactosidase was obtained from < 250
nucleotides of 5'-flanking sequence containing the complete promoter of either
U1 snRNA gene or from the 750-nt cytomegalovirus promoter and enhancer regions. The
mRNA was accurately initiated at the U1 start site, efficiently spliced and polyadenylylated, and localized to polyribosomes. Recombinant adenovirus containing the U1b-lacZ chimeric gene transduced and expressed
beta-galactosidase efficiently in human 293 cells and airway epithelial cells in culture. Viral vectors containing
U1 snRNA promoters may be an attractive alternative to vectors containing viral promoters for persistent high-level expression of therapeutic genes or
proteins.