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Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements

Most current models of mRNA nuclear export in vertebrate cells assume that an mRNA must have specialized signals in order to be exported from the nucleus. Under such a scenario, mRNAs that lack these specialized signals would be shunted into a default pathway where they are retained in the nucleus a...

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Detalles Bibliográficos
Autores principales: Akef, Abdalla, Lee, Eliza S., Palazzo, Alexander F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604431/
https://www.ncbi.nlm.nih.gov/pubmed/26362019
http://dx.doi.org/10.1261/rna.051987.115
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author Akef, Abdalla
Lee, Eliza S.
Palazzo, Alexander F.
author_facet Akef, Abdalla
Lee, Eliza S.
Palazzo, Alexander F.
author_sort Akef, Abdalla
collection PubMed
description Most current models of mRNA nuclear export in vertebrate cells assume that an mRNA must have specialized signals in order to be exported from the nucleus. Under such a scenario, mRNAs that lack these specialized signals would be shunted into a default pathway where they are retained in the nucleus and eventually degraded. These ideas were based on the selective use of model mRNA reporters. For example, it has been shown that splicing promotes the nuclear export of certain model mRNAs, such as human β-globin, and that in the absence of splicing, the cDNA-derived mRNA is retained in the nucleus and degraded. Here we provide evidence that β-globin mRNA contains an element that actively retains it in the nucleus and degrades it. Interestingly, this nuclear retention activity can be overcome by increasing the length of the mRNA or by splicing. Our results suggest that contrary to many current models, the default pathway for most intronless RNAs is to be exported from the nucleus, unless the RNA contains elements that actively promote its nuclear retention.
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spelling pubmed-46044312015-11-01 Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements Akef, Abdalla Lee, Eliza S. Palazzo, Alexander F. RNA Article Most current models of mRNA nuclear export in vertebrate cells assume that an mRNA must have specialized signals in order to be exported from the nucleus. Under such a scenario, mRNAs that lack these specialized signals would be shunted into a default pathway where they are retained in the nucleus and eventually degraded. These ideas were based on the selective use of model mRNA reporters. For example, it has been shown that splicing promotes the nuclear export of certain model mRNAs, such as human β-globin, and that in the absence of splicing, the cDNA-derived mRNA is retained in the nucleus and degraded. Here we provide evidence that β-globin mRNA contains an element that actively retains it in the nucleus and degrades it. Interestingly, this nuclear retention activity can be overcome by increasing the length of the mRNA or by splicing. Our results suggest that contrary to many current models, the default pathway for most intronless RNAs is to be exported from the nucleus, unless the RNA contains elements that actively promote its nuclear retention. Cold Spring Harbor Laboratory Press 2015-11 /pmc/articles/PMC4604431/ /pubmed/26362019 http://dx.doi.org/10.1261/rna.051987.115 Text en © 2015 Akef et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by/4.0/ This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Akef, Abdalla
Lee, Eliza S.
Palazzo, Alexander F.
Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements
title Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements
title_full Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements
title_fullStr Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements
title_full_unstemmed Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements
title_short Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements
title_sort splicing promotes the nuclear export of β-globin mrna by overcoming nuclear retention elements
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604431/
https://www.ncbi.nlm.nih.gov/pubmed/26362019
http://dx.doi.org/10.1261/rna.051987.115
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