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Functional insights from a surface antigen mRNA-bound proteome

Trypanosoma brucei is the causative agent of human sleeping sickness. The parasites’ variant surface glycoprotein (VSG) enables them to evade adaptive immunity via antigenic variation. VSG comprises 10% of total cell protein and the high stability of VSG mRNA is essential for trypanosome survival. T...

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Autores principales: Melo do Nascimento, Larissa, Egler, Franziska, Arnold, Katharina, Papavasiliou, Nina, Clayton, Christine, Erben, Esteban
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051951/
https://www.ncbi.nlm.nih.gov/pubmed/33783358
http://dx.doi.org/10.7554/eLife.68136
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author Melo do Nascimento, Larissa
Egler, Franziska
Arnold, Katharina
Papavasiliou, Nina
Clayton, Christine
Erben, Esteban
author_facet Melo do Nascimento, Larissa
Egler, Franziska
Arnold, Katharina
Papavasiliou, Nina
Clayton, Christine
Erben, Esteban
author_sort Melo do Nascimento, Larissa
collection PubMed
description Trypanosoma brucei is the causative agent of human sleeping sickness. The parasites’ variant surface glycoprotein (VSG) enables them to evade adaptive immunity via antigenic variation. VSG comprises 10% of total cell protein and the high stability of VSG mRNA is essential for trypanosome survival. To determine how VSG mRNA stability is maintained, we used mRNA affinity purification to identify all its associated proteins. CFB2 (cyclin F-box protein 2), an unconventional RNA-binding protein with an F-box domain, was specifically enriched with VSG mRNA. We demonstrate that CFB2 is essential for VSG mRNA stability, describe cis acting elements within the VSG 3'-untranslated region that regulate the interaction, identify trans-acting factors that are present in the VSG messenger ribonucleoprotein particle, and mechanistically explain how CFB2 stabilizes the mRNA of this key pathogenicity factor. Beyond T. brucei, the mRNP purification approach has the potential to supply detailed biological insight into metabolism of relatively abundant mRNAs in any eukaryote.
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spelling pubmed-80519512021-04-21 Functional insights from a surface antigen mRNA-bound proteome Melo do Nascimento, Larissa Egler, Franziska Arnold, Katharina Papavasiliou, Nina Clayton, Christine Erben, Esteban eLife Microbiology and Infectious Disease Trypanosoma brucei is the causative agent of human sleeping sickness. The parasites’ variant surface glycoprotein (VSG) enables them to evade adaptive immunity via antigenic variation. VSG comprises 10% of total cell protein and the high stability of VSG mRNA is essential for trypanosome survival. To determine how VSG mRNA stability is maintained, we used mRNA affinity purification to identify all its associated proteins. CFB2 (cyclin F-box protein 2), an unconventional RNA-binding protein with an F-box domain, was specifically enriched with VSG mRNA. We demonstrate that CFB2 is essential for VSG mRNA stability, describe cis acting elements within the VSG 3'-untranslated region that regulate the interaction, identify trans-acting factors that are present in the VSG messenger ribonucleoprotein particle, and mechanistically explain how CFB2 stabilizes the mRNA of this key pathogenicity factor. Beyond T. brucei, the mRNP purification approach has the potential to supply detailed biological insight into metabolism of relatively abundant mRNAs in any eukaryote. eLife Sciences Publications, Ltd 2021-03-30 /pmc/articles/PMC8051951/ /pubmed/33783358 http://dx.doi.org/10.7554/eLife.68136 Text en © 2021, Melo do Nascimento et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Melo do Nascimento, Larissa
Egler, Franziska
Arnold, Katharina
Papavasiliou, Nina
Clayton, Christine
Erben, Esteban
Functional insights from a surface antigen mRNA-bound proteome
title Functional insights from a surface antigen mRNA-bound proteome
title_full Functional insights from a surface antigen mRNA-bound proteome
title_fullStr Functional insights from a surface antigen mRNA-bound proteome
title_full_unstemmed Functional insights from a surface antigen mRNA-bound proteome
title_short Functional insights from a surface antigen mRNA-bound proteome
title_sort functional insights from a surface antigen mrna-bound proteome
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051951/
https://www.ncbi.nlm.nih.gov/pubmed/33783358
http://dx.doi.org/10.7554/eLife.68136
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