title: Role of Acinus in regulating retinoic acid-responsive gene pre-mRNA splicing.
abstract: Acinus-S' is a corepressor for retinoic acid receptor (RAR)-dependent gene transcription and has been suggested to be involved in RNA processing. In this study, the role of Acinus isoforms in regulating pre-mRNA splicing was explored using in vivo splicing assays. Both Acinus-L and Acinus-S', with the activity of Acinus-L higher than that of Acinus-S', increase the splicing of a retinoic acid (RA)-responsive minigene containing a weak 5' splice site but not a RA-responsive minigene containing a strong 5' splice site. RA treatment further enhances the splicing of the weak 5' splice site by Acinus in a dose- and time-dependent manner, suggesting a RA-dependent activity in addition to a RA-independent activity of Acinus. The RA-independent effect of Acinus occurs to varying degrees using minigene constructs containing several different promoters, while the RA-dependent splicing activity of Acinus is specific for transcripts derived from the minigene driven by a RA response element (RARE)-containing promoter. This suggests that the ligand-dependent splicing activity of Acinus is related to the RA-activated RAR bound to the RARE. The RRM domain is necessary for the RA-dependent splicing activity of Acinus and the RA-independent splicing activity of Acinus is repressed by RNPS1. Importantly, measurement of the splicing of endogenous human RARβ and Bcl-x in vivo demonstrates that Acinus stimulates the use of the weaker alternative 5' splice site of these two genes in a RA-dependent manner for RARβ and a RA-independent manner for Bcl-x. Taken together, these studies demonstrate that Acinus functions in both RAR-dependent splicing and RAR-dependent transcription.
authors.affiliation: Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Soprano
authors.forename: Dianne Robert
authors.initials: DR
authors.lastname: Soprano
mesh_terms: D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C121310:ACIN1 protein, human; D009687:Nuclear Proteins; D012322:RNA Precursors; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors