Overexpression of the alpha 2,6-sialyltransferase, ST6Gal I, in a low metastatic variant of a murine lymphoblastoid cell line is associated with appearance of a unique ST6Gal I mRNA

Multiple mRNA isoforms are generated from Siat1, the gene encoding ST6Gal I (beta-galactoside alpha 2,6-sialyltransferase, SiaT-1, ST6N, alpha 2,6ST). These isoforms, transcriptionally initiated from a number of physically di stinct promoter regions, differ only in the 5'-most untranslated region and share an identical ST6Gal I coding region. W16 cells, a spontaneous mutant from MDAY-D2, the highly metastatic murine lymphoid tumor cell line, is co nsiderably less metastatic and exhibits significantly slower tumor growth c haracteristics [R. Takano, E. Muchmore, and J. W. Dennis (1994) Glycobiolog y 4, 665-674]. Takano et al. further reported that ST6Gal I mRNA in W16 is elevated 40-fold compared to the parental cells. Here, by means of 5'-RACE analysis, we demonstrate a heretofore undocumented ST6Gal I mRNA form expre ssed in W16 cells. This ST6Gal I mRNA contains a novel 5'-most untranslated region with 96% sequence similarity to the retroviral-like transposable el ement, intracisternal particle A (IAP). This observation suggests the notio n that elevated ST6Gal I expression in W16 cells is the result of DNA rearr angement in the Siat1 locus. Atypical transcriptional activation of Siat1 i s the result of this IAP transposition. (C) 1999 Academic Press.