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Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome

During gene expression, RNA export factors are mainly known for driving nucleo-cytoplasmic transport. While early studies suggested that the exon junction complex (EJC) provides a binding platform for them, subsequent work proposed that they are only recruited by the cap binding complex to the 5′ en...

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Autores principales: Viphakone, Nicolas, Sudbery, Ian, Griffith, Llywelyn, Heath, Catherine G., Sims, David, Wilson, Stuart A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675937/
https://www.ncbi.nlm.nih.gov/pubmed/31104896
http://dx.doi.org/10.1016/j.molcel.2019.04.034
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author Viphakone, Nicolas
Sudbery, Ian
Griffith, Llywelyn
Heath, Catherine G.
Sims, David
Wilson, Stuart A.
author_facet Viphakone, Nicolas
Sudbery, Ian
Griffith, Llywelyn
Heath, Catherine G.
Sims, David
Wilson, Stuart A.
author_sort Viphakone, Nicolas
collection PubMed
description During gene expression, RNA export factors are mainly known for driving nucleo-cytoplasmic transport. While early studies suggested that the exon junction complex (EJC) provides a binding platform for them, subsequent work proposed that they are only recruited by the cap binding complex to the 5′ end of RNAs, as part of TREX. Using iCLIP, we show that the export receptor Nxf1 and two TREX subunits, Alyref and Chtop, are recruited to the whole mRNA co-transcriptionally via splicing but before 3′ end processing. Consequently, Alyref alters splicing decisions and Chtop regulates alternative polyadenylation. Alyref is recruited to the 5′ end of RNAs by CBC, and our data reveal subsequent binding to RNAs near EJCs. We demonstrate that eIF4A3 stimulates Alyref deposition not only on spliced RNAs close to EJC sites but also on single-exon transcripts. Our study reveals mechanistic insights into the co-transcriptional recruitment of mRNA export factors and how this shapes the human transcriptome.
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spelling pubmed-66759372019-08-06 Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome Viphakone, Nicolas Sudbery, Ian Griffith, Llywelyn Heath, Catherine G. Sims, David Wilson, Stuart A. Mol Cell Article During gene expression, RNA export factors are mainly known for driving nucleo-cytoplasmic transport. While early studies suggested that the exon junction complex (EJC) provides a binding platform for them, subsequent work proposed that they are only recruited by the cap binding complex to the 5′ end of RNAs, as part of TREX. Using iCLIP, we show that the export receptor Nxf1 and two TREX subunits, Alyref and Chtop, are recruited to the whole mRNA co-transcriptionally via splicing but before 3′ end processing. Consequently, Alyref alters splicing decisions and Chtop regulates alternative polyadenylation. Alyref is recruited to the 5′ end of RNAs by CBC, and our data reveal subsequent binding to RNAs near EJCs. We demonstrate that eIF4A3 stimulates Alyref deposition not only on spliced RNAs close to EJC sites but also on single-exon transcripts. Our study reveals mechanistic insights into the co-transcriptional recruitment of mRNA export factors and how this shapes the human transcriptome. Cell Press 2019-07-25 /pmc/articles/PMC6675937/ /pubmed/31104896 http://dx.doi.org/10.1016/j.molcel.2019.04.034 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Viphakone, Nicolas
Sudbery, Ian
Griffith, Llywelyn
Heath, Catherine G.
Sims, David
Wilson, Stuart A.
Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
title Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
title_full Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
title_fullStr Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
title_full_unstemmed Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
title_short Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
title_sort co-transcriptional loading of rna export factors shapes the human transcriptome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675937/
https://www.ncbi.nlm.nih.gov/pubmed/31104896
http://dx.doi.org/10.1016/j.molcel.2019.04.034
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