Expression of Multiple Sulfotransferase (SULT) 1C4 Transcript Variants in Developing Human Liver

Abstract

The cytosolic sulfotransferases (SULTs) are conjugating enzymes that catalyze the transfer of a sulfonate group from the cofactor 3′‐phosphoadenosine‐5′‐phosphosulfate to a variety of endogenous and xenobiotic substrates. The SULT1C subfamily includes three human genes, SULT1C2, SULT1C3, and SULT1C4, and relatively little is known about their expression and regulation or the functions of the enzymes. Previous studies have indicated that the human SULT1Cs are preferentially expressed during early life and are capable of metabolizing endogenous molecules such as thyroid and estrogen hormones, suggesting that these enzymes could play physiological roles during development. Several transcript variants (TVs) of SULT1C4 are indexed in GenBank, including the full‐length mRNA containing seven exons (TV1, NM_006588), a variant mRNA lacking exons 3 and 4 (TV2, NM_001321770), two non‐coding RNA variants (TV3, NR_135776 and TV4, NR_135779), and a predicted transcript variant (TVX1, XM_017003807). Using 5′‐RACE, RT‐PCR, and DNA sequencing, we detected TV1 and TV2, as well as a variant lacking only exon 3 (E3DEL) in Caco‐2 colorectal adenocarcinoma cells, HepaRG hepatic cells, and human liver specimens. The aim of the current study was to evaluate expression of the SULT1C4 TVs more thoroughly by (1) characterizing expression of individual SULT1C4 TVs in human liver specimens from prenatal, infant, and adult donors and (2) determining whether the individual mRNA variants can be translated into proteins. Using RT‐qPCR assays designed to quantify TV1, TV2, or E3DEL separately, all three variants were found to be primarily expressed in prenatal liver samples. The TV2 transcript lacking two exons was more abundant than the full‐length TV1, while E3DEL levels were minimal. In agreement with the RT‐qPCR data, RNA‐seq analysis of prenatal and pediatric liver specimens showed that TV1 and TV2 were both more abundant during early developmental stages. The RNA‐seq data also demonstrated that a non‐coding transcript variant (ENST00000494122.1) consisting of 2 exons only was expressed in the liver specimens and was predominantly expressed in prenatal liver. TV1 and TV2, but not E3DEL, were detected by western blot when plasmids expressing DDK‐tagged variants were transfected into HEK‐293T cells. These results indicate that at least four transcript variants of SULT1C4 are expressed in human liver, primarily during prenatal life, although only one of these (TV1) would encode a functional SULT enzyme. The physiological significance of this transcript diversity is unclear and will require further investigation.Support or Funding InformationSupported by NIH grants R01 ES022606 and P30 ES020957This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.