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The suppressive cap-binding complex factor 4EIP is required for normal differentiation
Trypanosoma brucei live in mammals as bloodstream forms and in the Tsetse midgut as procyclic forms. Differentiation from one form to the other proceeds via a growth-arrested stumpy form with low messenger RNA (mRNA) content and translation. The parasites have six eIF4Es and five eIF4Gs. EIF4E1 pair...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158607/ https://www.ncbi.nlm.nih.gov/pubmed/30124912 http://dx.doi.org/10.1093/nar/gky733 |
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author | Terrao, Monica Marucha, Kevin K Mugo, Elisha Droll, Dorothea Minia, Igor Egler, Franziska Braun, Johanna Clayton, Christine |
author_facet | Terrao, Monica Marucha, Kevin K Mugo, Elisha Droll, Dorothea Minia, Igor Egler, Franziska Braun, Johanna Clayton, Christine |
author_sort | Terrao, Monica |
collection | PubMed |
description | Trypanosoma brucei live in mammals as bloodstream forms and in the Tsetse midgut as procyclic forms. Differentiation from one form to the other proceeds via a growth-arrested stumpy form with low messenger RNA (mRNA) content and translation. The parasites have six eIF4Es and five eIF4Gs. EIF4E1 pairs with the mRNA-binding protein 4EIP but not with any EIF4G. EIF4E1 and 4EIP each inhibit expression when tethered to a reporter mRNA, but while tethered EIF4E1 suppresses only when 4EIP is present, suppression by tethered 4EIP does not require the interaction with EIF4E1. In growing bloodstream forms, 4EIP is preferentially associated with unstable mRNAs. Bloodstream- or procyclic-form trypanosomes lacking 4EIP have only a marginal growth disadvantage. Bloodstream forms without 4EIP are, however, defective in translation suppression during stumpy-form differentiation and cannot subsequently convert to growing procyclic forms. Intriguingly, the differentiation defect can be complemented by a truncated 4EIP that does not interact with EIF4E1. In contrast, bloodstream forms lacking EIF4E1 have a growth defect, stumpy formation seems normal, but they appear unable to grow as procyclic forms. We suggest that 4EIP and EIF4E1 fine-tune mRNA levels in growing cells, and that 4EIP contributes to translation suppression during differentiation to the stumpy form. |
format | Online Article Text |
id | pubmed-6158607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61586072018-10-02 The suppressive cap-binding complex factor 4EIP is required for normal differentiation Terrao, Monica Marucha, Kevin K Mugo, Elisha Droll, Dorothea Minia, Igor Egler, Franziska Braun, Johanna Clayton, Christine Nucleic Acids Res Molecular Biology Trypanosoma brucei live in mammals as bloodstream forms and in the Tsetse midgut as procyclic forms. Differentiation from one form to the other proceeds via a growth-arrested stumpy form with low messenger RNA (mRNA) content and translation. The parasites have six eIF4Es and five eIF4Gs. EIF4E1 pairs with the mRNA-binding protein 4EIP but not with any EIF4G. EIF4E1 and 4EIP each inhibit expression when tethered to a reporter mRNA, but while tethered EIF4E1 suppresses only when 4EIP is present, suppression by tethered 4EIP does not require the interaction with EIF4E1. In growing bloodstream forms, 4EIP is preferentially associated with unstable mRNAs. Bloodstream- or procyclic-form trypanosomes lacking 4EIP have only a marginal growth disadvantage. Bloodstream forms without 4EIP are, however, defective in translation suppression during stumpy-form differentiation and cannot subsequently convert to growing procyclic forms. Intriguingly, the differentiation defect can be complemented by a truncated 4EIP that does not interact with EIF4E1. In contrast, bloodstream forms lacking EIF4E1 have a growth defect, stumpy formation seems normal, but they appear unable to grow as procyclic forms. We suggest that 4EIP and EIF4E1 fine-tune mRNA levels in growing cells, and that 4EIP contributes to translation suppression during differentiation to the stumpy form. Oxford University Press 2018-09-28 2018-08-16 /pmc/articles/PMC6158607/ /pubmed/30124912 http://dx.doi.org/10.1093/nar/gky733 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Molecular Biology Terrao, Monica Marucha, Kevin K Mugo, Elisha Droll, Dorothea Minia, Igor Egler, Franziska Braun, Johanna Clayton, Christine The suppressive cap-binding complex factor 4EIP is required for normal differentiation |
title | The suppressive cap-binding complex factor 4EIP is required for normal differentiation |
title_full | The suppressive cap-binding complex factor 4EIP is required for normal differentiation |
title_fullStr | The suppressive cap-binding complex factor 4EIP is required for normal differentiation |
title_full_unstemmed | The suppressive cap-binding complex factor 4EIP is required for normal differentiation |
title_short | The suppressive cap-binding complex factor 4EIP is required for normal differentiation |
title_sort | suppressive cap-binding complex factor 4eip is required for normal differentiation |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158607/ https://www.ncbi.nlm.nih.gov/pubmed/30124912 http://dx.doi.org/10.1093/nar/gky733 |
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