Key result
Actinomycin D and severe heat shock drive RNA binding proteins into the Trypanosoma cruzi nucleolus.
This study demonstrates that the nucleolus in early divergent eukaryotes can sequester key mRNA metabolism factors in response to transcriptional stress.
Does not warrant changes in Chagas disease care; extends nucleolar sequestration of RNA factors to early divergent eukaryotes.
In this work we show that under Actinomycin D (ActD) treatment, several RNA Binding Proteins (RBPs) involved in mRNA metabolism are relocalized into the nucleolus in Trypanosoma cruzi as a specific stress response. ATP depletion as well as kinase inhibition markedly reduced the nucleolar localization response, suggesting that an energy-dependent transport modulated by the phosphorylation status of the parasite might be required. Deletion analyses in one of such proteins, TcSR62, showed that a domain bearing basic amino acids located in the COOH terminal region was sufficient to promote its nucleolar relocalization. Interestingly, we showed that in addition to RBPs, poly(A)+ RNA is also accumulated into the nucleolus in response to ActD treatment. Finally, we found out that nucleolar relocalization of RBPs is also triggered by severe heat shock in a reversible way. Together, these results suggest that the nucleolus of an early divergent eukaryote is either able to sequester key factors related to mRNA metabolism in response to transcriptional stress or behaves as a RBP processing center, arguing in favour to the hypothesis that the non-traditional features of the nucleolus could be acquired early during evolution.
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Názer et al. (2011) studied Trypanosoma cruzi infection (basic science model). Actinomycin D and Heat Shock vs. Untreated parasites was evaluated on Nucleolar localization of RNA Binding Proteins (e.g., TcSR62, TcPTB2). Actinomycin D treatment and severe heat shock induced the relocalization of several RNA Binding Proteins and poly(A)+ RNA into the nucleolus of Trypanosoma cruzi as a specific stress response.
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