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Posttranscriptional control and the role of RNA‐binding proteins in gene regulation in trypanosomatid protozoan parasites

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Abstract Trypanosomatids are unicellular eukaryotes responsible for severe diseases in humans. They exhibit a number of remarkable biological phenomena, especially at the RNA level. During their life cycles, they alternate between a mammalian host and an insect vector and undergo profound biochemical and morphological transformations in order to adapt to the different environments they find within one or the other host species. These changes are orchestrated by specific gene expression programs. In contrast to other organisms, trypanosomatids do not regulate RNA polymerase II‐dependent transcription initiation. Evidence so far indicates that the main control points in gene expression are mRNA degradation and translation. Recent studies have shown that RNA‐binding proteins (RBPs) play a critical role in the developmental regulation of mRNA and protein abundance. RBPs seem to bind to specific subsets of mRNAs encoding functionally related proteins. These ribonucleoprotein complexes may represent posttranscriptional operons or regulons that are able to control the fate of multiple mRNAs simultaneously. We suggest that trypanosomatids transduce environmental signals into mRNA and protein abundance through posttranslational modification of RBPs. Copyright © 2010 John Wiley & Sons, Ltd. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease

Distinctive features of RNA metabolism in trypanosomatids. A simplified representation of a Trypanosoma brucei cell is shown, together with a list of remarkable processes involved in RNA transcription, processing, and maturation.

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Posttranscriptional RNA operons (PTRO) and regulation of gene expression in trypanosomatids. Recent studies have shown that trypanosomal RNA‐binding proteins (RBPs) are associated with specific subsets of transcripts encoding functionally related proteins. These ribonucleoprotein complexes could act as PTROs, by which a single RBP is able to regulate simultaneously the fate of many mRNAs in response to environmental cues. Only four examples are described in the figure; see main text, further reading and Refs 75,78,81 for further possibilities. Extracellular signals known to trigger differentiation programs are transduced to mRNA/protein abundance via phosphorylation (or other kinds of posttranslational modification) of RBPs. (a) An RBP changes its binding properties and associates to a different mRNA subset upon phosphorylation. This association can promote the stabilization, degradation, or translation of target transcripts depending on the RBP (see main text). (b) Phosphorylation of a destabilizing RBP results in the stabilization of target transcripts either because of a loss of affinity or to the sequestration of the RBP in the nucleus or in cytosolic granules. (c) Regulation of mRNA localization. Ribonucleoprotein complexes become associated with P‐bodies, stress granules, or polysomes upon phosphorylation of an RBP. Alternatively, phosphorylation of an RBP in polysomes can lead to polysome dissociation and degradation of target transcripts. (d) Phosphorylation of an RBP that usually resides inside the nucleus promotes export to the cytosol. The RBP is now free to bind to target mRNAs, which leads to stabilization or enhanced translation.

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Gene transcription and pre‐mRNA processing in trypanosomatids. A chromosome is represented with three polycistronic transcription units (PTUs) separated by strand switch regions (SSRs). Transcription initiates at SSRs between two divergent PTUs and ends at SSRs between two convergent PTUs. Histone variants found in convergent SSRs are different from those associated with divergent SSRs. Therefore, PTUs are thought to be delimited by compact chromatin at convergent SSRs and open chromatin at divergent SSRs. See main text and Refs 2,12 for details.

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RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA in Disease and Development > RNA in Disease

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