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World J Biol Chem. Feb 26, 2016; 7(1): 146-157
Published online Feb 26, 2016. doi: 10.4331/wjbc.v7.i1.146
Regulation of RNA binding proteins in trypanosomatid protozoan parasites
María Albertina Romaniuk, Gabriela Cervini, Alejandro Cassola
María Albertina Romaniuk, Gabriela Cervini, Alejandro Cassola, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, 1650 San Martín, Provincia de Buenos Aires, Argentina
Author contributions: Romaniuk MA generated the tables and reviewed the manuscript; Cervini G reviewed the manuscript; Cassola A designed the aim of the review, wrote the manuscript and generated the tables.
Supported by The Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) to Alejandro Cassola.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alejandro Cassola, PhD, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, 1650 San Martín, Provincia de Buenos Aires, Argentina. acassola@iibintech.com.ar
Telephone: +54-11-40061500 Fax: +54-11-40061559
Received: May 28, 2015
Peer-review started: June 1, 2015
First decision: August 8, 2015
Revised: October 1, 2015
Accepted: January 27, 2016
Article in press: January 29, 2016
Published online: February 26, 2016
Processing time: 273 Days and 16.8 Hours
Abstract

Posttranscriptional mechanisms have a critical role in the overall outcome of gene expression. These mechanisms are especially relevant in protozoa from the genus Trypanosoma, which is composed by death threatening parasites affecting people in Sub-saharan Africa or in the Americas. In these parasites the classic view of regulation of transcription initiation to modulate the products of a given gene cannot be applied. This is due to the presence of transcription start sites that give rise to long polycistronic units that need to be processed costranscriptionally by trans-splicing and polyadenylation to give mature monocistronic mRNAs. Posttranscriptional mechanisms such as mRNA degradation and translational repression are responsible for the final synthesis of the required protein products. In this context, RNA-binding proteins (RBPs) in trypanosomes have a relevant role as modulators of mRNA abundance and translational repression by associating to the 3’ untranslated regions in mRNA. Many different RBPs have been proposed to modulate cohorts of mRNAs in trypanosomes. However, the current understanding of their functions lacks a dynamic view on the different steps at which these RBPs are regulated. Here, we discuss different evidences to propose regulatory events for different RBPs in these parasites. These events vary from regulated developmental expression, to biogenesis of cytoplasmic ribonucleoprotein complexes in the nucleus, and condensation of RBPs and mRNA into large cytoplasmic granules. Finally, we discuss how newly identified posttranslational modifications of RBPs and mRNA metabolism-related proteins could have an enormous impact on the modulation of mRNA abundance. To understand these modifications is especially relevant in these parasites due to the fact that the enzymes involved could be interesting targets for drug therapy.

Keywords: Trypanosoma; Posttranscriptional gene expression; Ribonucleoprotein complexes; RNA-binding protein; Developmental regulation; Sleeping sickness; Posttranslational modification; Phosphorylation; Chagas disease

Core tip: We discuss several ways to regulate the function of RNA-binding proteins in trypanosomes. We highlight the propensity of these proteins to engage in interactions with other proteins and RNA, resulting in the formation of large reversible aggregates induced by environmental stress. Finally, the possible role of posttranslational modifications on the function of these proteins is discussed in the context of recent high-throughput proteomic evidences.