title: RNA seeds higher-order assembly of FUS protein.
abstract: The abundant nuclear RNA binding protein FUS binds the C-terminal domain (CTD) of RNA polymerase II in an RNA-dependent manner, affecting Ser2 phosphorylation and transcription. Here, we examine the mechanism of this process and find that RNA binding nucleates the formation of higher-order FUS ribonucleoprotein assemblies that bind the CTD. Both the low-complexity domain and the arginine-glycine rich domain of FUS contribute to assembly. The assemblies appear fibrous by electron microscopy and have characteristics of β zipper structures. These results support the emerging view that the pathologic protein aggregation seen in neurodegenerative diseases such as amyotrophic lateral sclerosis may occur via the exaggeration of functionally important assemblies of RNA binding proteins.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Schwartz
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Xueyin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Podell
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA. Electronic address: thomas.cech@colorado.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics*; D012319:RNA Polymerase II / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D012313:RNA; D012319:RNA Polymerase II; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; D000097584:DNA Methyltransferase 3B