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Interaction of 7SK with the Smn complex modulates snRNP production

Gene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machi...

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Autores principales: Ji, Changhe, Bader, Jakob, Ramanathan, Pradhipa, Hennlein, Luisa, Meissner, Felix, Jablonka, Sibylle, Mann, Matthias, Fischer, Utz, Sendtner, Michael, Briese, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904863/
https://www.ncbi.nlm.nih.gov/pubmed/33627647
http://dx.doi.org/10.1038/s41467-021-21529-1
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author Ji, Changhe
Bader, Jakob
Ramanathan, Pradhipa
Hennlein, Luisa
Meissner, Felix
Jablonka, Sibylle
Mann, Matthias
Fischer, Utz
Sendtner, Michael
Briese, Michael
author_facet Ji, Changhe
Bader, Jakob
Ramanathan, Pradhipa
Hennlein, Luisa
Meissner, Felix
Jablonka, Sibylle
Mann, Matthias
Fischer, Utz
Sendtner, Michael
Briese, Michael
author_sort Ji, Changhe
collection PubMed
description Gene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.
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spelling pubmed-79048632021-03-11 Interaction of 7SK with the Smn complex modulates snRNP production Ji, Changhe Bader, Jakob Ramanathan, Pradhipa Hennlein, Luisa Meissner, Felix Jablonka, Sibylle Mann, Matthias Fischer, Utz Sendtner, Michael Briese, Michael Nat Commun Article Gene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand. Nature Publishing Group UK 2021-02-24 /pmc/articles/PMC7904863/ /pubmed/33627647 http://dx.doi.org/10.1038/s41467-021-21529-1 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ji, Changhe
Bader, Jakob
Ramanathan, Pradhipa
Hennlein, Luisa
Meissner, Felix
Jablonka, Sibylle
Mann, Matthias
Fischer, Utz
Sendtner, Michael
Briese, Michael
Interaction of 7SK with the Smn complex modulates snRNP production
title Interaction of 7SK with the Smn complex modulates snRNP production
title_full Interaction of 7SK with the Smn complex modulates snRNP production
title_fullStr Interaction of 7SK with the Smn complex modulates snRNP production
title_full_unstemmed Interaction of 7SK with the Smn complex modulates snRNP production
title_short Interaction of 7SK with the Smn complex modulates snRNP production
title_sort interaction of 7sk with the smn complex modulates snrnp production
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904863/
https://www.ncbi.nlm.nih.gov/pubmed/33627647
http://dx.doi.org/10.1038/s41467-021-21529-1
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