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FUS interacts with nuclear matrix-associated protein SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription.
Sci Rep. 2016 10 12; 6:35195.SR

Abstract

FUS (Fused-in-Sarcoma) is a multifunctional DNA/RNA binding protein linked to familial amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). Since FUS is localized mainly in the nucleus with nucleo-cytoplasmic shuttling, it is critical to understand physiological functions in the nucleus to clarify pathogenesis. Here we report a yeast two-hybrid screening identified FUS interaction with nuclear matrix-associated protein SAFB1 (scaffold attachment factor B1). FUS and SAFB1, abundant in chromatin-bound fraction, interact in a DNA-dependent manner. N-terminal SAP domain of SAFB1, a DNA-binding motif, was required for its localization to chromatin-bound fraction and splicing regulation. In addition, depletion of SAFB1 reduced FUS's localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif. FUS and SAFB1 also interact with Androgen Receptor (AR) regulating ligand-dependent transcription. Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates. These findings indicate SAFB1 could be a FUS's functional platform in chromatin compartment to regulate RNA splicing and ligand-dependent transcription and shed light on the etiological significance of nuclear matrix-associated proteins in ALS pathogenesis.

Authors+Show Affiliations

Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba, Japan.Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27731383

Citation

Yamaguchi, Atsushi, and Keisuke Takanashi. "FUS Interacts With Nuclear Matrix-associated Protein SAFB1 as Well as Matrin3 to Regulate Splicing and Ligand-mediated Transcription." Scientific Reports, vol. 6, 2016, p. 35195.
Yamaguchi A, Takanashi K. FUS interacts with nuclear matrix-associated protein SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription. Sci Rep. 2016;6:35195.
Yamaguchi, A., & Takanashi, K. (2016). FUS interacts with nuclear matrix-associated protein SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription. Scientific Reports, 6, 35195. https://doi.org/10.1038/srep35195
Yamaguchi A, Takanashi K. FUS Interacts With Nuclear Matrix-associated Protein SAFB1 as Well as Matrin3 to Regulate Splicing and Ligand-mediated Transcription. Sci Rep. 2016 10 12;6:35195. PubMed PMID: 27731383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FUS interacts with nuclear matrix-associated protein SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription. AU - Yamaguchi,Atsushi, AU - Takanashi,Keisuke, Y1 - 2016/10/12/ PY - 2016/07/06/received PY - 2016/09/26/accepted PY - 2016/10/13/entrez PY - 2016/10/13/pubmed PY - 2018/4/25/medline SP - 35195 EP - 35195 JF - Scientific reports JO - Sci Rep VL - 6 N2 - FUS (Fused-in-Sarcoma) is a multifunctional DNA/RNA binding protein linked to familial amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). Since FUS is localized mainly in the nucleus with nucleo-cytoplasmic shuttling, it is critical to understand physiological functions in the nucleus to clarify pathogenesis. Here we report a yeast two-hybrid screening identified FUS interaction with nuclear matrix-associated protein SAFB1 (scaffold attachment factor B1). FUS and SAFB1, abundant in chromatin-bound fraction, interact in a DNA-dependent manner. N-terminal SAP domain of SAFB1, a DNA-binding motif, was required for its localization to chromatin-bound fraction and splicing regulation. In addition, depletion of SAFB1 reduced FUS's localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif. FUS and SAFB1 also interact with Androgen Receptor (AR) regulating ligand-dependent transcription. Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates. These findings indicate SAFB1 could be a FUS's functional platform in chromatin compartment to regulate RNA splicing and ligand-dependent transcription and shed light on the etiological significance of nuclear matrix-associated proteins in ALS pathogenesis. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/27731383/FUS_interacts_with_nuclear_matrix_associated_protein_SAFB1_as_well_as_Matrin3_to_regulate_splicing_and_ligand_mediated_transcription_ L2 - http://dx.doi.org/10.1038/srep35195 DB - PRIME DP - Unbound Medicine ER -