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

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.

Basal Splicing Factors Regulate the Stability of Mature mRNAs in Trypanosomes

“…Many of these regulated genes were shown to be differentially regulated during cycling between the two hosts. Our data support the existence of RNA operons whose co-expression dictates the transcriptome during parasite differentiation (43,61).…”

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

“…Regulation of transcription initiation by RNA polymerase II is minimal (Martínez-Calvillo et al 2010;Günzl 2012). The control of protein abundance and function during the parasite lifecycle is mediated predominantly through post-transcriptional mechanisms such as mRNA stability and availability, translational efficiency, post-translational modification, and protein stability (Clayton and Shapira 2007;Fernandez-Moya and Estevez 2010;Kramer 2012).…”

The essential polysome-associated RNA-binding protein RBP42 targets mRNAs involved in Trypanosoma brucei energy metabolism

“…In trypanosomes, cis-acting elements have been identified mainly in 39 UTRs of stage-specific or cell cyclespecific mRNAs (Fernandez-Moya and Estevez 2010;Kramer and Carrington 2011). Some of the most extensively studied stage-specific mRNAs in trypanosomes are the procyclin mRNAs (Acosta-Serrano et al 2001).…”