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Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites

Gle1 is a nucleocytoplasmic shuttling protein with well-documented cytoplasmic roles as a modulator of ATP-dependent DEAD-box RNA helicases involved in messenger (m)RNA export, translation initiation and termination, and stress granule dynamics. Here, we identify a novel nuclear role for Gle1 during...

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Autores principales: Sharma, Manisha, Wente, Susan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851961/
https://www.ncbi.nlm.nih.gov/pubmed/32755435
http://dx.doi.org/10.1091/mbc.E20-03-0215
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author Sharma, Manisha
Wente, Susan R.
author_facet Sharma, Manisha
Wente, Susan R.
author_sort Sharma, Manisha
collection PubMed
description Gle1 is a nucleocytoplasmic shuttling protein with well-documented cytoplasmic roles as a modulator of ATP-dependent DEAD-box RNA helicases involved in messenger (m)RNA export, translation initiation and termination, and stress granule dynamics. Here, we identify a novel nuclear role for Gle1 during transcription termination. In HeLa cells treated with a peptide that disrupts Gle1 nucleocytoplasmic shuttling, we detected nuclear accumulation of specific mRNAs with elongated 3′-UTR (untranslated region). Enriched mRNAs were nascently transcribed and accumulated in the nucleus due to a change in transcription state and not due to altered nuclear export. Whereas Gle1 shuttling inhibition did not appear to perturb nuclear DDX19 functions, it did result in increased DDX1 nucleoplasmic localization and decreased DDX1 interactions with Gle1 and the pre-mRNA cleavage stimulation factor CstF-64. An increase in nuclear R-loop signal intensity was also observed with diminished Gle1 shuttling, as well as colocalization of Gle1 at R-loops. Taken together, these studies reveal a nuclear role for Gle1 in coordinating DDX1 function in transcription termination complexes.
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spelling pubmed-78519612021-02-05 Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites Sharma, Manisha Wente, Susan R. Mol Biol Cell Articles Gle1 is a nucleocytoplasmic shuttling protein with well-documented cytoplasmic roles as a modulator of ATP-dependent DEAD-box RNA helicases involved in messenger (m)RNA export, translation initiation and termination, and stress granule dynamics. Here, we identify a novel nuclear role for Gle1 during transcription termination. In HeLa cells treated with a peptide that disrupts Gle1 nucleocytoplasmic shuttling, we detected nuclear accumulation of specific mRNAs with elongated 3′-UTR (untranslated region). Enriched mRNAs were nascently transcribed and accumulated in the nucleus due to a change in transcription state and not due to altered nuclear export. Whereas Gle1 shuttling inhibition did not appear to perturb nuclear DDX19 functions, it did result in increased DDX1 nucleoplasmic localization and decreased DDX1 interactions with Gle1 and the pre-mRNA cleavage stimulation factor CstF-64. An increase in nuclear R-loop signal intensity was also observed with diminished Gle1 shuttling, as well as colocalization of Gle1 at R-loops. Taken together, these studies reveal a nuclear role for Gle1 in coordinating DDX1 function in transcription termination complexes. The American Society for Cell Biology 2020-10-01 /pmc/articles/PMC7851961/ /pubmed/32755435 http://dx.doi.org/10.1091/mbc.E20-03-0215 Text en © 2020 Sharma and Wente. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Sharma, Manisha
Wente, Susan R.
Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites
title Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites
title_full Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites
title_fullStr Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites
title_full_unstemmed Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites
title_short Nucleocytoplasmic shuttling of Gle1 impacts DDX1 at transcription termination sites
title_sort nucleocytoplasmic shuttling of gle1 impacts ddx1 at transcription termination sites
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851961/
https://www.ncbi.nlm.nih.gov/pubmed/32755435
http://dx.doi.org/10.1091/mbc.E20-03-0215
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