Three genes that encode human beta-galactoside alpha 2,3-sialyltransferases. Structural analysis and chromosomal...

Area of Science:

• Biochemistry
• Genetics
• Molecular Biology

Background:

• Alpha 2,3-linked sialic acid synthesis is mediated by beta-galactoside alpha 2,3-sialyltransferases (SiaT-4), encoded by three genes.
• Beta-galactoside alpha 2,6-sialyltransferase (SiaT-1) is encoded by a single gene.

Purpose of the Study:

• To investigate the relationship and genomic organization of the SiaT-4 genes.
• To characterize the structure and function of the SiaT-4a gene and its protein product.

Main Methods:

• Human-mouse somatic cell hybrid analysis to determine gene localization.
• Isolation and characterization of human SiaT-4a cDNA from submaxillary glands.
• 5'-RACE analysis to determine the 5'-untranslated region.
• Expression of the catalytic domain in transfected cells.
• Isolation and examination of genomic sequences for SiaT-4a.

Main Results:

• The three SiaT-4 genes (SIAT4A, SIAT4B, SIAT4C) are located on human chromosomes 8, 1 (p21-p34), and 11 (q23.3-qter), respectively.
• Human SiaT-4a cDNA possesses a long 5'-untranslated leader (1 kb).
• The expressed catalytic domain of SiaT-4a successfully synthesized sialic acid alpha 2,3 to Gal(beta 1,3)GalNAc-R.
• The SiaT-4a gene is composed of seven exons, with introns interrupting conserved sialylmotif domains, similar to the SiaT-1 gene.

Conclusions:

• The SiaT-4 genes are dispersed throughout the human genome.
• The SiaT-4a gene exhibits a complex exon-intron structure, with introns affecting conserved functional domains.
• The findings provide insights into the genetic regulation and evolution of sialyltransferases.