title: RNA association or phosphorylation of the RS domain prevents aggregation of RS domain-containing proteins.
abstract: Domains rich in alternating arginine and serine residues (RS domains) are found in a large number of eukaryotic proteins involved in several cellular processes. According to the prevailing view RS domains function as protein interaction domains, thereby promoting the assembly of higher-order cellular structures. Furthermore, recent data demonstrated that the RS regions of several SR splicing factors directly contact the pre-mRNA in a nonsequence specific but functionally important fashion. Using a variety of biochemical approaches, we now demonstrate that the RS domains of three proteins, not directly associated with the splicing reaction, such as lamin b receptor, acinus and peroxisome proliferator-activated receptor gamma coactivator-1 alpha, associate mainly with nuclear RNA and that this association is conducive in retaining the proteins in a soluble form. Phosphorylation by SRPK1 prevents RNA association, yet it greatly increases the fraction of the proteins recovered in soluble form, thereby mimicking the RNA effect. Based on these results we propose that the tendency to self-associate and form aggregates is a general property of RS domain-containing proteins and could be attributed to their disordered structure. RNA binding or SRPK1-mediated phosphorylation prevents aggregation and may serve to modulate the RS domain interaction modes.
authors.affiliation: Laboratory of Biochemistry, Department of Chemistry, The Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Nikolakaki
authors.forename: Victoria
authors.initials: V
authors.lastname: Drosou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sanidas
authors.forename: Philippos
authors.initials: P
authors.lastname: Peidis
authors.forename: Thomais
authors.initials: T
authors.lastname: Papamarcaki
authors.forename: Lilia M
authors.initials: LM
authors.lastname: Iakoucheva
authors.forename: Thomas
authors.initials: T
authors.lastname: Giannakouros
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D006801:Humans; D015636:Magnesium Chloride / Q000737:chemistry; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012326:RNA Splicing; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000097682:Lamin B Receptor
chemical_list: D001120:Arginine; D015636:Magnesium Chloride; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012313:RNA; D018160:Receptors, Cytoplasmic and Nuclear; D012694:Serine; D014157:Transcription Factors; D000097682:Lamin B Receptor; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1