title: Association of UBP1 to ribonucleoprotein complexes is regulated by interaction with the trypanosome ortholog of the human multifunctional P32 protein.
abstract: Regulation of gene expression in trypanosomatid parasitic protozoa is mainly achieved posttranscriptionally. RNA-binding proteins (RBPs) associate to 3' untranslated regions in mRNAs through dedicated domains such as the RNA recognition motif (RRM). Trypanosoma cruzi UBP1 (TcUBP1) is an RRM-type RBP involved in stabilization/degradation of mRNAs. TcUBP1 uses its RRM to associate with cytoplasmic mRNA and to mRNA granules under starvation stress. Here, we show that under starvation stress, TcUBP1 is tightly associated with condensed cytoplasmic mRNA granules. Conversely, under high nutrient/low density-growing conditions, TcUBP1 ribonucleoprotein (RNP) complexes are lax and permeable to mRNA degradation and disassembly. After dissociating from mRNA, TcUBP1 can be phosphorylated only in unstressed parasites. We have identified TcP22, the ortholog of mammalian P32/C1QBP, as an interactor of TcUBP1 RRM. Overexpression of TcP22 decreased the number of TcUBP1 granules in starved parasites in vivo. Endogenous TcUBP1 RNP complexes could be dissociated in vitro by addition of recombinant TcP22, a condition stimulating TcUBP1 phosphorylation. Biochemical and in silico analysis revealed that TcP22 interacts with the RNA-binding surface of TcUBP1 RRM. We propose a model for the decondensation of TcUBP1 RNP complexes in T. cruzi through direct interaction with TcP22 and phosphorylation.
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cassola
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: María Albertina
authors.initials: MA
authors.lastname: Romaniuk
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: Debora
authors.initials: D
authors.lastname: Primrose
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cervini
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: Iván
authors.initials: I
authors.lastname: D'Orso
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: Alberto Carlos
authors.initials: AC
authors.lastname: Frasch
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002457:Cell Extracts; D006801:Humans; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D000067776:RNA Recognition Motif Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins; D012261:Ribonucleoproteins / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000378:metabolism*
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D002457:Cell Extracts; D024101:Mitochondrial Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; C500732:UBP1 protein, Trypanosoma cruzi