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The two eIF4A helicases in Trypanosoma brucei are functionally distinct
Protozoan parasites belonging to the family Trypanosomatidae are characterized by an unusual pathway for the production of mRNAs via polycistronic transcription and trans-splicing of a 5′ capped mini-exon which is linked to the 3′ cleavage and polyadenylation of the upstream transcript. However, lit...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459412/ https://www.ncbi.nlm.nih.gov/pubmed/16687655 http://dx.doi.org/10.1093/nar/gkl290 |
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author | Dhalia, Rafael Marinsek, Nina Reis, Christian R. S. Katz, Rodolfo Muniz, João R. C. Standart, Nancy Carrington, Mark de Melo Neto, Osvaldo P. |
author_facet | Dhalia, Rafael Marinsek, Nina Reis, Christian R. S. Katz, Rodolfo Muniz, João R. C. Standart, Nancy Carrington, Mark de Melo Neto, Osvaldo P. |
author_sort | Dhalia, Rafael |
collection | PubMed |
description | Protozoan parasites belonging to the family Trypanosomatidae are characterized by an unusual pathway for the production of mRNAs via polycistronic transcription and trans-splicing of a 5′ capped mini-exon which is linked to the 3′ cleavage and polyadenylation of the upstream transcript. However, little is known of the mechanism of protein synthesis in these organisms, despite their importance as agents of a number of human diseases. Here we have investigated the role of two Trypanosoma brucei homologues of the translation initiation factor eIF4A (in the light of subsequent experiments these were named as TbEIF4AI and TbEIF4AIII). eIF4A, a DEAD-box RNA helicase, is a subunit of the translation initiation complex eIF4F which binds to the cap structure of eukaryotic mRNA and recruits the small ribosomal subunit. TbEIF4AI is a very abundant predominantly cytoplasmic protein (over 1 × 10(5) molecules/cell) and depletion to ∼10% of normal levels through RNA interference dramatically reduces protein synthesis one cell cycle following double-stranded RNA induction and stops cell proliferation. In contrast, TbEIF4AIII is a nuclear, moderately expressed protein (∼1–2 × 10(4) molecules/cell), and its depletion stops cellular proliferation after approximately four cell cycles. Ectopic expression of a dominant negative mutant of TbEIF4AI, but not of TbEIF4AIII, induced a slow growth phenotype in transfected cells. Overall, our results suggest that only TbEIF4AI is involved in protein synthesis while the properties and sequence of TbEIF4AIII indicate that it may be the orthologue of eIF4AIII, a component of the exon junction complex in mammalian cells. |
format | Text |
id | pubmed-1459412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-14594122006-05-15 The two eIF4A helicases in Trypanosoma brucei are functionally distinct Dhalia, Rafael Marinsek, Nina Reis, Christian R. S. Katz, Rodolfo Muniz, João R. C. Standart, Nancy Carrington, Mark de Melo Neto, Osvaldo P. Nucleic Acids Res Article Protozoan parasites belonging to the family Trypanosomatidae are characterized by an unusual pathway for the production of mRNAs via polycistronic transcription and trans-splicing of a 5′ capped mini-exon which is linked to the 3′ cleavage and polyadenylation of the upstream transcript. However, little is known of the mechanism of protein synthesis in these organisms, despite their importance as agents of a number of human diseases. Here we have investigated the role of two Trypanosoma brucei homologues of the translation initiation factor eIF4A (in the light of subsequent experiments these were named as TbEIF4AI and TbEIF4AIII). eIF4A, a DEAD-box RNA helicase, is a subunit of the translation initiation complex eIF4F which binds to the cap structure of eukaryotic mRNA and recruits the small ribosomal subunit. TbEIF4AI is a very abundant predominantly cytoplasmic protein (over 1 × 10(5) molecules/cell) and depletion to ∼10% of normal levels through RNA interference dramatically reduces protein synthesis one cell cycle following double-stranded RNA induction and stops cell proliferation. In contrast, TbEIF4AIII is a nuclear, moderately expressed protein (∼1–2 × 10(4) molecules/cell), and its depletion stops cellular proliferation after approximately four cell cycles. Ectopic expression of a dominant negative mutant of TbEIF4AI, but not of TbEIF4AIII, induced a slow growth phenotype in transfected cells. Overall, our results suggest that only TbEIF4AI is involved in protein synthesis while the properties and sequence of TbEIF4AIII indicate that it may be the orthologue of eIF4AIII, a component of the exon junction complex in mammalian cells. Oxford University Press 2006 2006-05-10 /pmc/articles/PMC1459412/ /pubmed/16687655 http://dx.doi.org/10.1093/nar/gkl290 Text en © The Author 2006. Published by Oxford University Press. All rights reserved |
spellingShingle | Article Dhalia, Rafael Marinsek, Nina Reis, Christian R. S. Katz, Rodolfo Muniz, João R. C. Standart, Nancy Carrington, Mark de Melo Neto, Osvaldo P. The two eIF4A helicases in Trypanosoma brucei are functionally distinct |
title | The two eIF4A helicases in Trypanosoma brucei are functionally distinct |
title_full | The two eIF4A helicases in Trypanosoma brucei are functionally distinct |
title_fullStr | The two eIF4A helicases in Trypanosoma brucei are functionally distinct |
title_full_unstemmed | The two eIF4A helicases in Trypanosoma brucei are functionally distinct |
title_short | The two eIF4A helicases in Trypanosoma brucei are functionally distinct |
title_sort | two eif4a helicases in trypanosoma brucei are functionally distinct |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459412/ https://www.ncbi.nlm.nih.gov/pubmed/16687655 http://dx.doi.org/10.1093/nar/gkl290 |
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