Association of UBP1 to ribonucleoprotein complexes is regulated by interaction with the trypanosome ortholog of the human multifunctional P32 protein

Alejandro Cassola, María Albertina Romaniuk, Debora Primrose, Gabriela Cervini, Iván D'Orso, Alberto Carlos Frasch

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 cruziUBP1 (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.

Original languageEnglish (US)
Pages (from-to)1079-1096
Number of pages18
JournalMolecular Microbiology
Volume97
Issue number6
DOIs
StatePublished - Sep 1 2015

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Trypanosoma
Ribonucleoproteins
Trypanosomiasis
Proteins
Messenger RNA
RNA-Binding Proteins
RNA Stability
Starvation
Parasites
Phosphorylation
Cytoplasmic Granules
Gene Expression Regulation
3' Untranslated Regions
Computer Simulation

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Association of UBP1 to ribonucleoprotein complexes is regulated by interaction with the trypanosome ortholog of the human multifunctional P32 protein. / Cassola, Alejandro; Romaniuk, María Albertina; Primrose, Debora; Cervini, Gabriela; D'Orso, Iván; Frasch, Alberto Carlos.

In: Molecular Microbiology, Vol. 97, No. 6, 01.09.2015, p. 1079-1096.

Research output: Contribution to journalArticle

Cassola, Alejandro ; Romaniuk, María Albertina ; Primrose, Debora ; Cervini, Gabriela ; D'Orso, Iván ; Frasch, Alberto Carlos. / Association of UBP1 to ribonucleoprotein complexes is regulated by interaction with the trypanosome ortholog of the human multifunctional P32 protein. In: Molecular Microbiology. 2015 ; Vol. 97, No. 6. pp. 1079-1096.
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