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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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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. |
format | Online Article Text |
id | pubmed-8051951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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