Ubikviliini 2 UBQLN2. Mutaatio tässä geenissä linkkiytyy ALS- tautiin.

https://pubmed.ncbi.nlm.nih.gov/30442662/

  2018 Dec 4;115(49):E11485-E11494.

doi: 10.1073/pnas.1811997115. Epub 2018 Nov 15.

Ubiquilin 2 Modulates ALS/FTD-linked FUS-RNA Complex Dynamics and Stress Granule Formation

Elizabeth J Alexander  ^{1   2} , Amirhossein Ghanbari Niaki 

PMID: 30442662
PMCID: PMC6298105
DOI: 10.1073/pnas.1811997115
Free PMC article

Abstract

The ubiquitin-like protein ubiquilin 2 (UBQLN2) has been genetically and pathologically linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but its normal cellular functions are not well understood. In a search for UBQLN2-interacting proteins, we found an enrichment of stress granule (SG) components, including ALS/FTD-linked heterogeneous ribonucleoprotein fused in sarcoma (FUS) (FUS gene 16p11.2) . Through the use of an optimized SG detection method, we observed UBQLN2 and its interactors at SGs. A low complexity, Sti1-like repeat region in UBQLN2 was sufficient for its localization to SGs. Functionally, UBQLN2 negatively regulated SG formation. UBQLN2 increased the dynamics of FUS-RNA interaction and promoted the fluidity of FUS-RNA complexes at a single-molecule level. This solubilizing effect corresponded to a dispersal of FUS liquid droplets in vitro and a suppression of FUS SG formation in cells. ALS-linked mutations in UBQLN2 reduced its association with FUS and impaired its function in regulating FUS-RNA complex dynamics and SG formation. These results reveal a previously unrecognized role for UBQLN2 in regulating the early stages of liquid-liquid phase separation by directly modulating the fluidity of protein-RNA complexes and the dynamics of SG formation.

Keywords: ALS; FTD; FUS; stress granule; ubiquilin 2.

Conflict of interest statement

The authors declare no conflict of interest.

UBQLN2 geeni, NEDD4-sitova proteiini N4BP4 , ALS15

Aliases for UBQLN2 Gene

• GeneCards Symbol: UBQLN2 ²
• Ubiquilin 2 ^{2 3 5}
• N4BP4 ^{2 3 4 5}
• PLIC2 ^{2 3 4 5}
• PLIC-2 ^{2 4 5}
• Chap1 ^{2 4 5}
• Protein Linking IAP With Cytoskeleton 2 ^{3 4}
• Ubiquitin-Like Product Chap1/Dsk2 ^{3 4}
• Ubiquilin-2 ^{3 4}
• CHAP1/DSK2 ^{2 5}
• RIHFB2157 ^{2 5}

• LIC-2 ^{2 5}
• Dsk2 ^{2 5}
• NEDD4 Binding Protein 4 ²
• Nedd4 Binding Protein 4 ³
• DSK2 Homolog ⁴
• HRIHFB2157 ³
• HPLIC-2 ⁴
• ALS15 ³
• CHAP1 ³
• DSK2 ³

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