RETROVIRAL INSERTIONS IN THE MURINE HIS-1 LOCUS ACTIVATE THE EXPRESSION OF A NOVEL RNA THAT LACKS AN EXTENSIVE OPEN READING FRAME

The His-1 locus is a common site of viral insertion in murine myeloid leukemias induced by the wild mouse ecotropic retrovirus, CasBrM. In t his report, we describe the cloning of a novel gene at the His-1 locus and show that His-1 expression is associated with the transformed phe notype. Northern (RNA) blot analysis identified His-1 transcripts in f our transformed myeloid cell lines but in no normal tissues examined. Two of these cell lines were derived from retrovirus-induced myeloid l eukemias that harbor integrated proviruses which drive His-1 gene expr ession by promoter insertion. The two other cell lines expressed a dis crete 3-kb His-1 RNA that is derived from a novel gene consisting of t hree exons that span 6 kb on mouse chromosome 2. The His-1 gene is con served as a single-copy sequence in multiple vertebrate species and is expressed as a spliced and polyadenylated RNA. A protein-coding regio n is not evident from analysis of the His-1 sequence because of the pr esence of multiple small open reading frames, none of which are greate r than 219 bp. This lack of an extensive open reading frame is an unus ual feature that is shared by other RNA molecules believed to function in the absence of translation.