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Vol 49(2015) N 2 p. 287-294; DOI 10.1134/S002689331501015X Full Text

A.V. Rozhkova1, I.B. Filippenkov1, O.Yu. Sudarkina1, S.A. Limborska1,2, L.V. Dergunova1,2*

Alternative promoters located in SGMS1 gene introns participate in regulation of its expression in human tissues

1Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182 Russia
2Research Institute of Cerebrovascular Pathology and Stroke, Pirogov Russian National Research Medical University, Moscow, 117997 Russia

*lvdergunova@mail.ru
Received - 2014-07-18; Accepted - 2014-08-25

Sphingomyelin synthase 1 (SMS1) is a vitally important enzyme responsible for the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide in eukaryotic cells. Previously, we have investigated the structure of the human gene SGMS1 in detail and identified a lot of its transcripts. We have found mRNA isoforms that differ in their 5'-untranslated regions (UTRs) and encode a full-length protein. We have also detected the transcripts that arise from an alternative exon combination and comprise a coding region of the gene and a 3'-UTR. Computer analysis revealed that the synthesis of the transcripts differing in 5'-UTRs starts from different SGMS1 gene promoters. In the present study performed using the real-time PCR, we demonstrated that the contents of five alternative gene transcripts that differ in their 5'-UTRs is substantially dissimilar in the studied human tissues. The transcripts synthesized under the control of the distal promoter comprising exon 1 were the most abundant. The content of the transcripts comprising 5'-terminal exons, the synthesis of which is enabled by the promoters localized in the gene introns, is lower. Different contents of gene SGMS1 transcripts that differ in 5'-UTRs indicates that the use of certain alternative promoters is tissue-specific and, apparently, strictly regulated. The 5'-UTR structures of the SGMS1 gene transcripts controlled by alternative promoters differ significantly, which indicates that the gene functioning is regulated at the posttranscriptional level.

human sphingomyelin synthase 1, alternative promoters, 5'-UTR, gene expression, level of transcripts, real-time PCR



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