The mouse sphingomyelin synthase 1 (SMS1) gene is alternatively spliced to yield multiple transcripts and proteins

Sphingomyelin synthase 1 (SMS1) is a recently identified 413-residue protein that plays a critical role in sphingolipid metabolism by catalyzing the conversion of ceramide and phosphatidylcholine to sphingomyelin and diacylglycerol (DAG). We have previously reported the isolation of a mouse SMS1 encoding cDNA that contains a unique 5′ UTR sequence. Three other mouse SMS1 cDNAs that differed in their 5′ and 3′ non-coding sequences were present in GenBank. In order to ascertain the origin of the unique 5′ and 3′ UTR sequences, we analyzed the structure of the mouse SMS1 gene. Analysis of the four different SMS1 cDNA sequences and of the corresponding mouse genomic fragment revealed that the SMS1 gene consists of 16 exons that are alternatively spliced to produce 4 different mRNAs (SMS1α1, SMS1α2, SMS1β and SMS1γ) and 3 different proteins (SMS1α, SMS1β and SMS1γ). RT-PCR was used to demonstrate that all four SMS1 cDNAs represent expressed transcripts that show distinctly different tissue distributions. Transcripts for SMS1α1, SMS1α2 and SMS1β were found to increase in response to the pro-apoptotic effects of TNF-α. Finally, using a yeast-based assay, we confirmed that SMS1α prevents the growth inhibitory effects of Bax but SMS1β neither prevents nor enhances the effects of Bax or of SMS1α. Taken together these results demonstrate the complexity of SMS1 gene structure, expression and function.