Translation initiation in Leishmania major: characterisation of multiple eIF4F subunit homologues

Dhália, Rafael; Reis, Christian Robson de Souza; Freire, Eden R.; Rocha, Pollyanna O.; Katz, Rodolfo; Muniz, J.R.C.; Standart, Nancy; Neto, Osvaldo P. de Melo

doi:10.1016/j.molbiopara.2004.12.001

Cited by 83 publications

(125 citation statements)

References 75 publications

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“…The eIF4E protein that recognizes the cap 0 structure as a first step in mRNA translation fits this description, and searches using the yeast eIF4E sequence yielded a set of five potential eIF4E family members that are present in T. brucei (Tb4EIF4E), T. cruzi, and Leishmania spp. Of this set, four have been identified and studied to varying degrees by other groups (Yoffe et al 2004(Yoffe et al , 2006(Yoffe et al , 2009Dhalia et al 2005;Freire et al 2011). A sixth homolog was identified by reciprocal BLAST with the uncharacterized TbEIF4E sequence.…”

Section: Two New Members Of the Kinetoplastid Eif4e-homolog Familymentioning

confidence: 99%

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

Freire

Vashisht

Malvezzi

et al. 2014

RNA

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Members of the eIF4E mRNA cap-binding family are involved in translation and the modulation of transcript availability in other systems as part of a three-component complex including eIF4G and eIF4A. The kinetoplastids possess four described eIF4E and five eIF4G homologs. We have identified two new eIF4E family proteins in Trypanosoma brucei, and define distinct complexes associated with the fifth member, TbEIF4E5. The cytosolic TbEIF4E5 protein binds cap 0 in vitro. TbEIF4E5 was found in association with two of the five TbEIF4Gs. TbIF4EG1 bound TbEIF4E5, a 47.5-kDa protein with two RNA-binding domains, and either the regulatory protein 14-3-3 II or a 117.5-kDa protein with guanylyltransferase and methyltransferase domains in a potentially dynamic interaction. The TbEIF4G2/TbEIF4E5 complex was associated with a 17.9-kDa hypothetical protein and both 14-3-3 variants I and II. Knockdown of TbEIF4E5 resulted in the loss of productive cell movement, as evidenced by the inability of the cells to remain in suspension in liquid culture and the loss of social motility on semisolid plating medium, as well as a minor reduction of translation. Cells appeared lethargic, as opposed to compromised in flagellar function per se. The minimal use of transcriptional control in kinetoplastids requires these organisms to implement downstream mechanisms to regulate gene expression, and the TbEIF4E5/TbEIF4G1/117.5-kDa complex in particular may be a key player in that process. We suggest that a pathway involved in cell motility is affected, directly or indirectly, by one of the TbEIF4E5 complexes.

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Section: Two New Members Of the Kinetoplastid Eif4e-homolog Familymentioning

confidence: 99%

“…have four eIF4E homologs (EIF4E) and five eIF4G homologs (EIF4G) (Dhalia et al 2005;Freire et al 2011;. In some cases, the respective interacting partners have been identified: EIF4E3 binds to EIF4G4, and EIF4E4 binds to EIF4G3 (Yoffe et al 2009;Freire et al 2011;, whereas EIF4E1 appears to lack an EIF4G partner (Zinoviev et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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

Freire

Vashisht

Malvezzi

et al. 2014

RNA

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“…In this process, the 5´ cap interacts with a multi-protein complex named eIF4F, formed by at least three proteins: eIF4A, an ATP-dependent RNA helicase; eIF4E, the capbinding protein; and eIF4G, a scaffold protein that interacts with the poly(A) binding protein, IF4A and IF4E. Data mining on the Leishmania major genome database has revealed four eIF4Es (LmEIF4E1-4), two eIF4As (LmEIF4A1-2) and five eIF4Gs (LmEIF4G1-5) putative proteins [41].…”

Section: Initiation Factorsmentioning

confidence: 99%

“…Five different proteins harboring MIF4G domain are present in the genome of L. major, named LmIF4G-1 to LmIF4G-5 [41]. All of them have clearly predictable orthologues in T. brucei and T. cruzi.…”

Section: Trypanosomatid If4gmentioning

confidence: 99%

“…All of them have clearly predictable orthologues in T. brucei and T. cruzi. From these, and based on different functional assays including pulldown, yeast-two hybrid and polysome profiles, LmIF4G-3 seems to be the most probable orthologous with a major role in translation initiation [41,58]. Interestingly, phylogeny inference shows that trypanosomatid IF4G proteins form a separate clade, implying several gene duplication events into the trypanosomatid lineage ( Figure 10).…”

Section: Trypanosomatid If4gmentioning

confidence: 99%

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Ribosomes from Trypanosomatids: Unique Structural and Functional Properties

Ayub¹,

Lapadula²,

Hoebeke³

et al. 2012

Cell-Free Protein Synthesis

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Additional information is available at the end of the chapter http://dx.doi.org/10.5772/48336 IntroductionTrypanosomatids are a monophyletic group of protozoa that diverged early from the eukaryotic lineage, constituting valuable model organisms for studying variability in different highly conserved processes including protein synthesis. Moreover, several species of trypanosomatids are causing agents of endemic diseases in the third world. There are many evidences suggesting that translation in these organisms shows important differences with that of model organisms such as yeast and mammals. These unique features, which have a great potential relevance for both basic and applied research, will be discussed in this chapter. Structural analysis Cryo-electron microscopy map of Trypanosoma cruzi ribosome: Unique features of the rRNAUsing the cryo-electron microscopy (cryo-EM) technique, a 12Å resolution density map of the T. cruzi 80S ribosome has been constructed [1]. The overall structure of the T. cruzi 80S ribosome exhibits well defined small (40S) and large (60S) subunits (Figure 1). Some of the landmark characteristics of the ribosome structure can be identified in the density map. Compared with the 80S ribosome from yeast, both the small and large ribosomal subunits from T. cruzi are larger, mainly due to the size of the ribosomal RNA molecules. T. cruzi rRNA (18S rRNA: 2,315 nt and 28S rRNA: 4,151 nt) is one-fifth larger than yeast rRNA (18S rRNA: 1,798 nt; 25S rRNA: 3,392 nt) in total number of nucleotides.Although the T. cruzi 80S ribosome possesses conserved ribosomal structures, it exhibits many distinctive structural features in both the small and large subunits. Compared with other eukaryotic ribosomes, the T. cruzi ribosomal 40S subunit appears expanded, due to the addition of a large piece of density adjacent to the platform region ( Figure 1). As can be seen in the secondary structure of the T. cruzi 18S rRNA (Figure 2), this extra density must be attributed to two large expansion segments (ES) in domain II of the 18S rRNA, ES6 and ES7, designated as insertions of helices 21 and 26. These are the two largest ES in the T. cruzi 18S rRNA, involving 504 and 147 nucleotides, respectively.

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

Fernández‐Moya

Estévez

2010

WIREs RNA

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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.

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Translation initiation in Leishmania major: characterisation of multiple eIF4F subunit homologues

Cited by 83 publications

References 75 publications

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

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

Ribosomes from Trypanosomatids: Unique Structural and Functional Properties

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

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