Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.

Nonsense-mediated mRNA decay (NMD), which is best known for degrading mRNAs with premature termination codons (PTCs), is thought to be triggered by aberrant translation termination at stop codons located in an environment of the mRNP that is devoid of signals necessary for proper termination. In mam...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Raphael Joncourt, Andrea B Eberle, Simone C Rufener, Oliver Mühlemann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a2e4f7eb2974f25bab21006b5189bf9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4a2e4f7eb2974f25bab21006b5189bf9
record_format	dspace
spelling	oai:doaj.org-article:4a2e4f7eb2974f25bab21006b5189bf92021-11-25T06:03:33ZEukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.1932-620310.1371/journal.pone.0104391https://doaj.org/article/4a2e4f7eb2974f25bab21006b5189bf92014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25148142/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Nonsense-mediated mRNA decay (NMD), which is best known for degrading mRNAs with premature termination codons (PTCs), is thought to be triggered by aberrant translation termination at stop codons located in an environment of the mRNP that is devoid of signals necessary for proper termination. In mammals, the cytoplasmic poly(A)-binding protein 1 (PABPC1) has been reported to promote correct termination and therewith antagonize NMD by interacting with the eukaryotic release factors 1 (eRF1) and 3 (eRF3). Using tethering assays in which proteins of interest are recruited as MS2 fusions to a NMD reporter transcript, we show that the three N-terminal RNA recognition motifs (RRMs) of PABPC1 are sufficient to antagonize NMD, while the eRF3-interacting C-terminal domain is dispensable. The RRM1-3 portion of PABPC1 interacts with eukaryotic initiation factor 4G (eIF4G) and tethering of eIF4G to the NMD reporter also suppresses NMD. We identified the interactions of the eIF4G N-terminus with PABPC1 and the eIF4G core domain with eIF3 as two genetically separable features that independently enable tethered eIF4G to inhibit NMD. Collectively, our results reveal a function of PABPC1, eIF4G and eIF3 in translation termination and NMD suppression, and they provide additional evidence for a tight coupling between translation termination and initiation.Raphael JoncourtAndrea B EberleSimone C RufenerOliver MühlemannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104391 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raphael Joncourt Andrea B Eberle Simone C Rufener Oliver Mühlemann Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.
description	Nonsense-mediated mRNA decay (NMD), which is best known for degrading mRNAs with premature termination codons (PTCs), is thought to be triggered by aberrant translation termination at stop codons located in an environment of the mRNP that is devoid of signals necessary for proper termination. In mammals, the cytoplasmic poly(A)-binding protein 1 (PABPC1) has been reported to promote correct termination and therewith antagonize NMD by interacting with the eukaryotic release factors 1 (eRF1) and 3 (eRF3). Using tethering assays in which proteins of interest are recruited as MS2 fusions to a NMD reporter transcript, we show that the three N-terminal RNA recognition motifs (RRMs) of PABPC1 are sufficient to antagonize NMD, while the eRF3-interacting C-terminal domain is dispensable. The RRM1-3 portion of PABPC1 interacts with eukaryotic initiation factor 4G (eIF4G) and tethering of eIF4G to the NMD reporter also suppresses NMD. We identified the interactions of the eIF4G N-terminus with PABPC1 and the eIF4G core domain with eIF3 as two genetically separable features that independently enable tethered eIF4G to inhibit NMD. Collectively, our results reveal a function of PABPC1, eIF4G and eIF3 in translation termination and NMD suppression, and they provide additional evidence for a tight coupling between translation termination and initiation.
format	article
author	Raphael Joncourt Andrea B Eberle Simone C Rufener Oliver Mühlemann
author_facet	Raphael Joncourt Andrea B Eberle Simone C Rufener Oliver Mühlemann
author_sort	Raphael Joncourt
title	Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.
title_short	Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.
title_full	Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.
title_fullStr	Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.
title_full_unstemmed	Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.
title_sort	eukaryotic initiation factor 4g suppresses nonsense-mediated mrna decay by two genetically separable mechanisms.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4a2e4f7eb2974f25bab21006b5189bf9
work_keys_str_mv	AT raphaeljoncourt eukaryoticinitiationfactor4gsuppressesnonsensemediatedmrnadecaybytwogeneticallyseparablemechanisms AT andreabeberle eukaryoticinitiationfactor4gsuppressesnonsensemediatedmrnadecaybytwogeneticallyseparablemechanisms AT simonecrufener eukaryoticinitiationfactor4gsuppressesnonsensemediatedmrnadecaybytwogeneticallyseparablemechanisms AT olivermuhlemann eukaryoticinitiationfactor4gsuppressesnonsensemediatedmrnadecaybytwogeneticallyseparablemechanisms
_version_	1718414219830886400

Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.

Ejemplares similares