The RNA-binding protein FUS is chaperoned and imported into the nucleus by a network of import receptors
| Autor: | Dorothee Dormann, Mario Hofweber, Imke Baade, Ralph H. Kehlenbach, Saskia Hutten, Erin L. Sternburg, Marius Pörschke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
FTD frontotemporal dementia RNA-binding protein importins RG/RGG motifs Nuclear Localization Signals Receptors Cytoplasmic and Nuclear Biochemistry T tyrosine PY proline–tyrosine R arginine TNPO transportin Chemistry NTR nuclear transport receptor LCD low-complexity domain TB transport buffer beta Karyopherins EGFP enhanced green fluorescent protein Cell biology LLPS liquid–liquid phase separation Transportin 1 RBP RNA-binding protein transportin RGG3 arginine–glycine–rich Research Article Protein Binding rps ribosomal proteins SEC size-exclusion chromatography Importin nuclear transport Karyopherins unme unmethylated PRMT1 protein arginine N-methyltransferase 1 03 medical and health sciences Stress granule S supernatant Ribosomal protein CIRBP cold-inducible RNA-binding protein Humans Molecular Biology Xpo 4 exportin 4 CRM1 chromosome region maintenance 1 Cell Nucleus 030102 biochemistry & molecular biology Cell Biology SG stress granule TNPO3 transportin-3 TNPO1 transportin-1 030104 developmental biology MBP maltose binding protein NLS nuclear localization signal RNA-Binding Protein FUS BSA bovine serum albumin Nuclear transport phase separation TDP-43 TAR DNA-binding protein 43 RS arginine–serine fused in sarcoma (FUS) Nuclear localization sequence TNPO2 transportin-2 DAPI 4′ 6-diamidino-2-phenylindole FUS fused in sarcoma HeLa Cells Molecular Chaperones |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Fused in sarcoma (FUS) is a predominantly nuclear RNA-binding protein with key functions in RNA processing and DNA damage repair. Defects in nuclear import of FUS have been linked to severe neurodegenerative diseases; hence, it is of great interest to understand this process and how it is dysregulated in disease. Transportin-1 (TNPO1) and the closely related transportin-2 have been identified as major nuclear import receptors of FUS. They bind to the C-terminal nuclear localization signal of FUS and mediate the protein's nuclear import and at the same time also suppress aberrant phase transitions of FUS in the cytoplasm. Whether FUS can utilize other nuclear transport receptors for the purpose of import and chaperoning has not been examined so far. Here, we show that FUS directly binds to different import receptors in vitro. FUS formed stable complexes not only with TNPO1 but also with transportin-3, importin β, importin 7, or the importin β/7 heterodimer. Binding of these alternative import receptors required arginine residues within FUS-RG/RGG motifs and was weakened by arginine methylation. Interaction with these importins suppressed FUS phase separation and reduced its sequestration into stress granules. In a permeabilized cell system, we further showed that transportin-3 had the capacity to import FUS into the nucleus, albeit with lower efficiency than TNPO1. Our data suggest that aggregation-prone RNA-binding proteins such as FUS may utilize a network of importins for chaperoning and import, similar to histones and ribosomal proteins. |
| Databáze: | OpenAIRE |
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