Multiple mRNA isoforms are generated from SIAT1, the gene encoding the beta-galactoside alpha 2,6-sialyltransferase (ST6Gal I, SiaT-1, ST6N, alpha 2,6ST). These isoforms are transcriptionally initiated from a number of physically distinct promoter regions. In human B-lymphocytic cells, two SIAT1 mRNA isoforms have been identified. In order to determine if additional SIAT1 mRNA isotypes exist, RNA from Louckes, a human cell line with the mature B-phenotype, was subjected to 5'-RACE analysis. In addition to the two previously characterized mRNA forms, three additional SIAT1 mRNA forms were identified. The new mRNA isoforms incorporate novel sequence blocks into their 5'-UT regions. The data strongly suggest that these novel sequence blocks originate from previously undocumented 5'-noncoding exons and are incorporated into mRNA by alternative splicing events and/or usage of additional transcriptional promoter regions. BLAST analysis reveals no similarity of these novel regions, Exons U, V, and W, to sequences in GenBank. The only exception is Exon V, which contains a portion of Alu, a repetitive element. The data suggest that two of these novel mRNA isotypes are likely to be minor components. However, one form may contribute significantly to the SIAT1 mRNA pool in Louckes cells.