title: Inhibition of SULT4A1 expression induces up-regulation of phototransduction gene expression in 72-hour postfertilization zebrafish larvae.
abstract: Sulfotransferase (SULT) 4A1 is an orphan enzyme that shares distinct structure and sequence similarities with other cytosolic SULTs. SULT4A1 is primarily expressed in neuronal tissue and is also the most conserved SULT, having been identified in every vertebrate investigated to date. Certain haplotypes of the SULT4A1 gene are correlated with higher baseline psychopathology in schizophrenic patients, but no substrate or function for SULT4A1 has yet been identified despite its high level of sequence conservation. In this study, deep RNA sequencing was used to search for alterations in gene expression in 72-hour postfertilization zebrafish larvae following transient SULT4A1 knockdown (KD) utilizing splice blocking morpholino oligonucleotides. This study demonstrates that transient inhibition of SULT4A1 expression in developing zebrafish larvae results in the up-regulation of several genes involved in phototransduction. SULT4A1 KD was verified by immunoblot analysis and quantitative real-time polymerase chain reaction (qPCR). Gene regulation changes identified by deep RNA sequencing were validated by qPCR. This study is the first identification of a cellular process whose regulation appears to be associated with SULT4A1 expression.
authors.affiliation: Departments of Pharmacology and Toxicology (F.C., H.T., J.P., C.N.F.), Medicine (D.C.), and Vision Sciences (T.K.), University of Alabama at Birmingham, Birmingham, Alabama; and R&D Systems, Minneapolis, Minnesota (C.M.E., Z.L.W.).
authors.forename: Frank
authors.initials: F
authors.lastname: Crittenden
authors.forename: Holly
authors.initials: H
authors.lastname: Thomas
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Ethen
authors.forename: Zhengliang L
authors.initials: ZL
authors.lastname: Wu
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Kraft
authors.forename: John M
authors.initials: JM
authors.lastname: Parant
authors.forename: Charles N
authors.initials: CN
authors.lastname: Falany
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D005123:Eye / Q000196:embryology / Q000378:metabolism; D005306:Fertilization; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007814:Larva; D055537:Light Signal Transduction / Q000235:genetics*; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D017386:Sequence Homology, Amino Acid; D015238:Sulfotransferases / Q000235:genetics / Q000502:physiology*; D059467:Transcriptome; D015854:Up-Regulation; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D060172:Morpholinos; D029961:Zebrafish Proteins; D012313:RNA; C000593012:SULT4A1 protein, zebrafish; D015238:Sulfotransferases