title: A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans.
abstract: The exosome complex is a major eukaryotic exoribonuclease that requires the SKI complex for its activity in the cytoplasm. In yeast, the Ski7 protein links both complexes, whereas a functional equivalent of the Ski7 has remained unknown in the human genome. Proteomic analysis revealed that a previously uncharacterized short splicing isoform of HBS1L (HBS1LV3) is the long-sought factor linking the exosome and SKI complexes in humans. In contrast, the canonical HBS1L variant, HBS1LV1, which acts as a ribosome dissociation factor, does not associate with the exosome and instead interacts with the mRNA surveillance factor PELOTA. Interestingly, both HBS1LV1 and HBS1LV3 interact with the SKI complex and HBS1LV1 seems to antagonize SKI/exosome supercomplex formation. HBS1LV3 contains a unique C-terminal region of unknown structure, with a conserved RxxxFxxxL motif responsible for exosome binding and may interact with the exosome core subunit RRP43 in a way that resembles the association between Rrp6 RNase and Rrp43 in yeast. HBS1LV3 or the SKI complex helicase (SKI2W) depletion similarly affected the transcriptome, deregulating multiple genes. Furthermore, half-lives of representative upregulated mRNAs were increased, supporting the involvement of HBS1LV3 and SKI2W in the same mRNA degradation pathway, essential for transcriptome homeostasis in the cytoplasm.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kalisiak
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Kuliński
authors.forename: Rafał
authors.initials: R
authors.lastname: Tomecki
authors.forename: Dominik
authors.initials: D
authors.lastname: Cysewski
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Pietras
authors.forename: Aleksander
authors.initials: A
authors.lastname: Chlebowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kowalska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Dziembowski
mesh_terms: D001665:Binding Sites; D003593:Cytoplasm / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex / Q000737:chemistry / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D000072756:Protein Conformation, alpha-Helical; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D063326:Exosome Multienzyme Ribonuclease Complex; D019204:GTP-Binding Proteins; C000628258:HBS1L protein, human