Trypanosoma brucei EIF4E2 cap-binding protein binds a homolog of the histone-mRNA stem-loop-binding protein
Trypanosomatids are parasitic protozoans characterized by several unique structural and metabolic processes that include exquisite mechanisms associated with gene expression and regulation. During the initiation of protein synthesis, for instance, mRNA selection for translation seems to be mediated by different eIF4F-like complexes, which may play a significant role in parasite adaptation to different hosts. In eukaryotes, the heterotrimeric eIF4F complex (formed by eIF4E, eIF4G, and eIF4A) mediates mRNA recognition and ribosome binding and participates in various translation regulatory events. Six eIF4Es and five eIF4Gs have been described in trypanosomatids with several of these forming different eIF4F-like complexes. This has raised questions about their role in differential mRNA translation. Here we have studied further TbEIF4E2, the least known eIF4E homologue from Trypanosoma brucei, and found that it is not associated with an eIF4G homolog. It is, however, associated with mature mRNAs and binds to a histone mRNA stem-loop-binding protein (SLBP), one of two Trypanosoma SLBP homologs (TbSLBP1 and TbSLBP2). TbSLBP1 is more similar to the mammalian counterpart while TbSLBP2 is exclusive to trypanosomatids and related organisms. TbSLBP2 binds to TbEIF4E2 through a conserved central region missing in other SLBP homologs. Both SLBPs, as well as TbEIF4E2, were found to localize to the cytoplasm. TbEIF4E2 and TbSLBP2 are differentially expressed during cell culture, being more abundant in early-log phase, with TbSLBP2 also showing cell-cycle dependent expression. The new data reinforce unique aspects of the trypanosomatid eIF4Es, with the TbEIF4E2–TbSLBP complex possibly having a role in differential selection of mRNAs containing stem-loop structures.
KeywordsSLBP Kinetoplastid mRNA cap SLBP Translation initiation factor
The authors thank Dr. Mark Carrington, from University of Cambridge (UK), and Dr. Steve Kelly, from Department of Plant Sciences, University of Oxford (UK) for providing the SLBP protein sequences from Euglena gracilis. We also thank Dr. Cássia Docena from the Núcleo de Plataformas Tecnológicas (NPT), Instituto Aggeu Magalhães, Fiocruz-PE, for the assistance in obtaining Immunofluorescence images. The anti-BiP and anti-TY antibodies were kind gifts from Jay Bangs and Keith Gull, respectively. This work was supported by a UCLA Stein-Oppenheimer award (D. C.), the National Institutes of Health (Grant numbers AI056034, AI073806, TW009035 to D. C. and N. S., Grant number GM089778 to J. W.), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil, Grant number 401282/2014-7) and Fundação Oswaldo Cruz-Fiocruz (Brazil). Funding was provided by Fogarty International Center (PAR-08-222).
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Conflict of interest
No potential conflicts of interest were disclosed.
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