Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes

Abstract By interacting with the mRNA 5′ cap, the translation initiation factor eIF4E plays a critical role in selecting mRNAs for protein synthesis in eukaryotic cells. Caf20 is a member of the family of proteins found across eukaryotes termed 4E-BPs, which compete with eIF4G for interaction with e...

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Autores principales:	Ebelechukwu C. Nwokoye, Eiman AlNaseem, Robert A. Crawford, Lydia M. Castelli, Martin D. Jennings, Christopher J. Kershaw, Graham D. Pavitt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a170f8d568954ea3bc06d0d1845d3a9b
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spelling	oai:doaj.org-article:a170f8d568954ea3bc06d0d1845d3a9b2021-12-02T16:10:38ZOverlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes10.1038/s41598-021-92931-42045-2322https://doaj.org/article/a170f8d568954ea3bc06d0d1845d3a9b2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92931-4https://doaj.org/toc/2045-2322Abstract By interacting with the mRNA 5′ cap, the translation initiation factor eIF4E plays a critical role in selecting mRNAs for protein synthesis in eukaryotic cells. Caf20 is a member of the family of proteins found across eukaryotes termed 4E-BPs, which compete with eIF4G for interaction with eIF4E. Caf20 independently interacts with ribosomes. Thus, Caf20 modulates the mRNA selection process via poorly understood mechanisms. Here we performed unbiased mutagenesis across Caf20 to characterise which regions of Caf20 are important for interaction with eIF4E and with ribosomes. Caf20 binding to eIF4E is entirely dependent on a canonical motif shared with other 4E-BPs. However, binding to ribosomes is weakened by mutations throughout the protein, suggesting an extended binding interface that partially overlaps with the eIF4E-interaction region. By using chemical crosslinking, we identify a potential ribosome interaction region on the ribosome surface that spans both small and large subunits and is close to a known interaction site of eIF3. The function of ribosome binding by Caf20 remains unclear.Ebelechukwu C. NwokoyeEiman AlNaseemRobert A. CrawfordLydia M. CastelliMartin D. JenningsChristopher J. KershawGraham D. PavittNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ebelechukwu C. Nwokoye Eiman AlNaseem Robert A. Crawford Lydia M. Castelli Martin D. Jennings Christopher J. Kershaw Graham D. Pavitt Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes
description	Abstract By interacting with the mRNA 5′ cap, the translation initiation factor eIF4E plays a critical role in selecting mRNAs for protein synthesis in eukaryotic cells. Caf20 is a member of the family of proteins found across eukaryotes termed 4E-BPs, which compete with eIF4G for interaction with eIF4E. Caf20 independently interacts with ribosomes. Thus, Caf20 modulates the mRNA selection process via poorly understood mechanisms. Here we performed unbiased mutagenesis across Caf20 to characterise which regions of Caf20 are important for interaction with eIF4E and with ribosomes. Caf20 binding to eIF4E is entirely dependent on a canonical motif shared with other 4E-BPs. However, binding to ribosomes is weakened by mutations throughout the protein, suggesting an extended binding interface that partially overlaps with the eIF4E-interaction region. By using chemical crosslinking, we identify a potential ribosome interaction region on the ribosome surface that spans both small and large subunits and is close to a known interaction site of eIF3. The function of ribosome binding by Caf20 remains unclear.
format	article
author	Ebelechukwu C. Nwokoye Eiman AlNaseem Robert A. Crawford Lydia M. Castelli Martin D. Jennings Christopher J. Kershaw Graham D. Pavitt
author_facet	Ebelechukwu C. Nwokoye Eiman AlNaseem Robert A. Crawford Lydia M. Castelli Martin D. Jennings Christopher J. Kershaw Graham D. Pavitt
author_sort	Ebelechukwu C. Nwokoye
title	Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes
title_short	Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes
title_full	Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes
title_fullStr	Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes
title_full_unstemmed	Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes
title_sort	overlapping regions of caf20 mediate its interactions with the mrna-5′cap-binding protein eif4e and with ribosomes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a170f8d568954ea3bc06d0d1845d3a9b
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Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes

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