Functional insights from a surface antigen mRNA-bound proteome

• Verfasst von: Melo do Nascimento, Larissa [VerfasserIn]
• Verfasst von: Falk, Franziska [VerfasserIn]
• Verfasst von: Arnold, Katharina [VerfasserIn]
• Verfasst von: Papavasiliou, Nina [VerfasserIn]
• Verfasst von: Clayton, Christine [VerfasserIn]
• Verfasst von: Erben, Esteban [VerfasserIn]
• Titel: Functional insights from a surface antigen mRNA-bound proteome
• Verf.angabe: Larissa Melo do Nascimento, Franziska Egler, Katharina Arnold, Nina Papavasiliou, Christine Clayton, Esteban Erben
• E-Jahr: 2021
• Jahr: 30 March 2021
• Umfang: 26 S.
• Fussnoten: Gesehen am 08.06.2021
• Titel Quelle: Enthalten in: eLife
• Ort Quelle: Cambridge : eLife Sciences Publications, 2012
• Jahr Quelle: 2021
• Band/Heft Quelle: 10(2021), Artikel-ID e68136, Seite 1-26
• ISSN Quelle: 2050-084X
• DOI: doi:10.7554/eLife.68136
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: antigenic variation
• Sach-SW: CFB2
• Sach-SW: F-box
• Sach-SW: RNA-binding proteins
• Sach-SW: Trypanosoma brucei
• Sach-SW: VSG
• K10plus-PPN: 1760000701

Abstract

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.