Translational repression of NMD targets by GIGYF2 and EIF4E2.

Translation of messenger RNAs (mRNAs) with premature termination codons produces truncated proteins with potentially deleterious effects. This is prevented by nonsense-mediated mRNA decay (NMD) of these mRNAs. NMD is triggered by ribosomes terminating upstream of a splice site marked by an exon-junc...

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Autores principales:	Boris Zinshteyn, Niladri K Sinha, Syed Usman Enam, Benjamin Koleske, Rachel Green
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fa5279b562774fcdb51142e48baba02b
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spelling	oai:doaj.org-article:fa5279b562774fcdb51142e48baba02b2021-12-02T20:03:30ZTranslational repression of NMD targets by GIGYF2 and EIF4E2.1553-73901553-740410.1371/journal.pgen.1009813https://doaj.org/article/fa5279b562774fcdb51142e48baba02b2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009813https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Translation of messenger RNAs (mRNAs) with premature termination codons produces truncated proteins with potentially deleterious effects. This is prevented by nonsense-mediated mRNA decay (NMD) of these mRNAs. NMD is triggered by ribosomes terminating upstream of a splice site marked by an exon-junction complex (EJC), but also acts on many mRNAs lacking a splice junction after their termination codon. We developed a genome-wide CRISPR flow cytometry screen to identify regulators of mRNAs with premature termination codons in K562 cells. This screen recovered essentially all core NMD factors and suggested a role for EJC factors in degradation of PTCs without downstream splicing. Among the strongest hits were the translational repressors GIGYF2 and EIF4E2. GIGYF2 and EIF4E2 mediate translational repression but not mRNA decay of a subset of NMD targets and interact with NMD factors genetically and physically. Our results suggest a model wherein recognition of a stop codon as premature can lead to its translational repression through GIGYF2 and EIF4E2.Boris ZinshteynNiladri K SinhaSyed Usman EnamBenjamin KoleskeRachel GreenPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 10, p e1009813 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Boris Zinshteyn Niladri K Sinha Syed Usman Enam Benjamin Koleske Rachel Green Translational repression of NMD targets by GIGYF2 and EIF4E2.
description	Translation of messenger RNAs (mRNAs) with premature termination codons produces truncated proteins with potentially deleterious effects. This is prevented by nonsense-mediated mRNA decay (NMD) of these mRNAs. NMD is triggered by ribosomes terminating upstream of a splice site marked by an exon-junction complex (EJC), but also acts on many mRNAs lacking a splice junction after their termination codon. We developed a genome-wide CRISPR flow cytometry screen to identify regulators of mRNAs with premature termination codons in K562 cells. This screen recovered essentially all core NMD factors and suggested a role for EJC factors in degradation of PTCs without downstream splicing. Among the strongest hits were the translational repressors GIGYF2 and EIF4E2. GIGYF2 and EIF4E2 mediate translational repression but not mRNA decay of a subset of NMD targets and interact with NMD factors genetically and physically. Our results suggest a model wherein recognition of a stop codon as premature can lead to its translational repression through GIGYF2 and EIF4E2.
format	article
author	Boris Zinshteyn Niladri K Sinha Syed Usman Enam Benjamin Koleske Rachel Green
author_facet	Boris Zinshteyn Niladri K Sinha Syed Usman Enam Benjamin Koleske Rachel Green
author_sort	Boris Zinshteyn
title	Translational repression of NMD targets by GIGYF2 and EIF4E2.
title_short	Translational repression of NMD targets by GIGYF2 and EIF4E2.
title_full	Translational repression of NMD targets by GIGYF2 and EIF4E2.
title_fullStr	Translational repression of NMD targets by GIGYF2 and EIF4E2.
title_full_unstemmed	Translational repression of NMD targets by GIGYF2 and EIF4E2.
title_sort	translational repression of nmd targets by gigyf2 and eif4e2.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fa5279b562774fcdb51142e48baba02b
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Translational repression of NMD targets by GIGYF2 and EIF4E2.

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