title: The SAP motif and C-terminal RS- and RD/E-rich region influences the sub-nuclear localization of Acinus isoforms.
abstract: Acinus has been reported to function in apoptosis, RNA processing and regulation of gene transcription including RA-dependent transcription. There are three different isoforms of Acinus termed Acinus-L, Acinus-S', and Acinus-S. The isoforms of Acinus differ in their N-terminus while the C-terminus is consistent in all isoforms. The sub-nuclear localization of Acinus-L and Acinus-S' was determined using fluorescence microscopy. Acinus-S' colocalizes with SC35 in nuclear speckles while Acinus-L localizes diffusely throughout the nucleoplasm. RA treatment has little effect on the sub-nuclear localization of Acinus-L and Acinus-S'. The domains/regions necessary for the distinct sub-nuclear localization of Acinus-L and Acinus-S' were identified. The speckled sub-nuclear localization of Acinus-S' is dependent on its C-terminal RS- and RD/E-rich region but is independent of the phosphorylation status of Ser-453 and Ser-604 within this region. The unique N-terminal SAP motif of Acinus-L is responsible for its diffuse localization in the nucleus. Moreover, the sub-nuclear localization of Acinus isoforms is affected by each other, which is determined by the combinatorial effect of the more potent SAP motif of Acinus-L and the C-terminal RS- and RD/E-rich region in all Acinus isoforms. The C-terminal RS- and RD/E-rich region of Acinus mediates the colocalization of Acinus isoforms as well as with its interacting protein RNPS1. In conclusion, the SAP motif is responsible for the difference in the nuclear localization between Acinus-L and Acinus-S'. This difference in the nuclear localization of Acinus-S' and Acinus-L may suggest that these two isoforms have different functional roles.
authors: Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140.
authors: Fang
authors: F
authors: Wang
authors: Karen S
authors: KS
authors: Wendling
authors: Kenneth J
authors: KJ
authors: Soprano
authors: Dianne Robert
authors: DR
authors: Soprano
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: C121310:ACIN1 protein, human; D002843:Chromatin; D009687:Nuclear Proteins; D020033:Protein Isoforms
keywords: ACINUS; NUCLEAR SPECKLES; RS DOMAIN; SAP MOTIF; SR/SR-RELATED PROTEINS