A weak upstream promoter gives rise to long human β-globin RNA molecules

The 5′ ends of most normal human β globin mRNA molecules correspond to a single transcription initiation site, often referred to as the "CAP" site (1-4). Using S₁ nuclease mapping and primer extension techniques, we have determined that a minority of β globin gene transcripts are longer at the 5′ ends. These longer molecules comprise about 10% of total β globin RNA molecules in normal human bone marrow cells and in peripheral blood reticulocytes. The long molecules are transcribed only from the sense strand of DNA and are probably spliced correctly. A DNA segment that includes imperfect "CCAAT" and "TATA" promoter-like sequences begins approximately 150 base pairs (bp) upstream from the normal β globin gene promoter; this "pseudo-promoter" may function in the initiation of the long globin RNA molecules.