A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans
| Autor: | Zbigniew Pietras, Rafal Tomecki, Andrzej Dziembowski, Aleksander Chlebowski, Dominik Cysewski, Tomasz M. Kulinski, Katarzyna Kowalska, Katarzyna Kalisiak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation alpha-Helical Cytoplasm RNase P Exosome complex RNA Splicing RNA Stability Biology Exosome 03 medical and health sciences 0302 clinical medicine GTP-Binding Proteins Exoribonuclease Genetics Humans Protein Isoforms RNA Messenger Ski complex Binding Sites Exosome Multienzyme Ribonuclease Complex Molecular biology mRNA surveillance Cell biology 030104 developmental biology HEK293 Cells RNA splicing TRAMP complex RNA 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|