Terrao, Monica, Marucha, Kevin K., Mugo, Elisha, Droll, Dorothea, Minia, Igor, Egler, Franziska, Braun, Johanna and Clayton, Christine ORCID: 0000-0002-6384-0731 (2018). The suppressive cap-binding complex factor 4EIP is required for normal differentiation. Nucleic Acids Res., 46 (17). S. 8993 - 9011. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Terrao, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marucha, Kevin K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mugo, ElishaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Droll, DorotheaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Minia, IgorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egler, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, JohannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clayton, ChristineUNSPECIFIEDorcid.org/0000-0002-6384-0731UNSPECIFIED
URN: urn:nbn:de:hbz:38-172385
DOI: 10.1093/nar/gky733
Journal or Publication Title: Nucleic Acids Res.
Volume: 46
Number: 17
Page Range: S. 8993 - 9011
Date: 2018
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1362-4962
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRYPANOSOMA-BRUCEI; GENE-EXPRESSION; TRANSLATION INITIATION; MESSENGER-RNAS; PHOSPHOGLYCERATE KINASE; POTENTIAL ROLES; EIF4E ISOFORMS; LIFE-CYCLE; PROTEIN; HOMOLOGMultiple languages
Biochemistry & Molecular BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17238

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