Overexpression of the alpha2,6-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 alpha2,6-sialyltransferase, SiaT-1, ST6N, alpha2,6ST). These isoforms, transcriptionally initiated from a number of physically distinct 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 considerably less metastatic and exhibits significantly slower tumor growth characteristics [R. Takano, E. Muchmore, and J. W. Dennis (1994) Glycobiology 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 expressed in W16 cells. This ST6Gal I mRNA contains a novel 5'-most untranslated region with 96% sequence similarity to the retroviral-like transposable element, intracisternal particle A (IAP). This observation suggests the notion that elevated ST6Gal I expression in W16 cells is the result of DNA rearrangement in the Siat1 locus. Atypical transcriptional activation of Siat1 is the result of this IAP transposition.
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N W
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Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263, USA.
Dennis
J W
JW
Lau
J T
JT
D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012799:Sialyltransferases / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase