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Succession of splicing regulatory elements determines cryptic 5΄ss functionality
A critical step in exon definition is the recognition of a proper splice donor (5΄ss) by the 5’ end of U1 snRNA. In the selection of appropriate 5΄ss, cis-acting splicing regulatory elements (SREs) are indispensable. As a model for 5΄ss recognition, we investigated cryptic 5΄ss selection within the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397162/ https://www.ncbi.nlm.nih.gov/pubmed/28039323 http://dx.doi.org/10.1093/nar/gkw1317 |
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author | Brillen, Anna-Lena Schöneweis, Katrin Walotka, Lara Hartmann, Linda Müller, Lisa Ptok, Johannes Kaisers, Wolfgang Poschmann, Gereon Stühler, Kai Buratti, Emanuele Theiss, Stephan Schaal, Heiner |
author_facet | Brillen, Anna-Lena Schöneweis, Katrin Walotka, Lara Hartmann, Linda Müller, Lisa Ptok, Johannes Kaisers, Wolfgang Poschmann, Gereon Stühler, Kai Buratti, Emanuele Theiss, Stephan Schaal, Heiner |
author_sort | Brillen, Anna-Lena |
collection | PubMed |
description | A critical step in exon definition is the recognition of a proper splice donor (5΄ss) by the 5’ end of U1 snRNA. In the selection of appropriate 5΄ss, cis-acting splicing regulatory elements (SREs) are indispensable. As a model for 5΄ss recognition, we investigated cryptic 5΄ss selection within the human fibrinogen Bβ-chain gene (FGB) exon 7, where we identified several exonic SREs that simultaneously acted on up- and downstream cryptic 5΄ss. In the FGB exon 7 model system, 5΄ss selection iteratively proceeded along an alternating sequence of U1 snRNA binding sites and interleaved SREs which in principle supported different 3’ exon ends. Like in a relay race, SREs either suppressed a potential 5΄ss and passed the splicing baton on or splicing actually occurred. From RNA-Seq data, we systematically selected 19 genes containing exons with silent U1 snRNA binding sites competing with nearby highly used 5΄ss. Extensive SRE analysis by different algorithms found authentic 5΄ss significantly more supported by SREs than silent U1 snRNA binding sites, indicating that our concept may permit generalization to a model for 5΄ss selection and 3’ exon end definition. |
format | Online Article Text |
id | pubmed-5397162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53971622017-04-24 Succession of splicing regulatory elements determines cryptic 5΄ss functionality Brillen, Anna-Lena Schöneweis, Katrin Walotka, Lara Hartmann, Linda Müller, Lisa Ptok, Johannes Kaisers, Wolfgang Poschmann, Gereon Stühler, Kai Buratti, Emanuele Theiss, Stephan Schaal, Heiner Nucleic Acids Res RNA A critical step in exon definition is the recognition of a proper splice donor (5΄ss) by the 5’ end of U1 snRNA. In the selection of appropriate 5΄ss, cis-acting splicing regulatory elements (SREs) are indispensable. As a model for 5΄ss recognition, we investigated cryptic 5΄ss selection within the human fibrinogen Bβ-chain gene (FGB) exon 7, where we identified several exonic SREs that simultaneously acted on up- and downstream cryptic 5΄ss. In the FGB exon 7 model system, 5΄ss selection iteratively proceeded along an alternating sequence of U1 snRNA binding sites and interleaved SREs which in principle supported different 3’ exon ends. Like in a relay race, SREs either suppressed a potential 5΄ss and passed the splicing baton on or splicing actually occurred. From RNA-Seq data, we systematically selected 19 genes containing exons with silent U1 snRNA binding sites competing with nearby highly used 5΄ss. Extensive SRE analysis by different algorithms found authentic 5΄ss significantly more supported by SREs than silent U1 snRNA binding sites, indicating that our concept may permit generalization to a model for 5΄ss selection and 3’ exon end definition. Oxford University Press 2017-04-20 2016-12-30 /pmc/articles/PMC5397162/ /pubmed/28039323 http://dx.doi.org/10.1093/nar/gkw1317 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | RNA Brillen, Anna-Lena Schöneweis, Katrin Walotka, Lara Hartmann, Linda Müller, Lisa Ptok, Johannes Kaisers, Wolfgang Poschmann, Gereon Stühler, Kai Buratti, Emanuele Theiss, Stephan Schaal, Heiner Succession of splicing regulatory elements determines cryptic 5΄ss functionality |
title | Succession of splicing regulatory elements determines cryptic 5΄ss functionality |
title_full | Succession of splicing regulatory elements determines cryptic 5΄ss functionality |
title_fullStr | Succession of splicing regulatory elements determines cryptic 5΄ss functionality |
title_full_unstemmed | Succession of splicing regulatory elements determines cryptic 5΄ss functionality |
title_short | Succession of splicing regulatory elements determines cryptic 5΄ss functionality |
title_sort | succession of splicing regulatory elements determines cryptic 5΄ss functionality |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397162/ https://www.ncbi.nlm.nih.gov/pubmed/28039323 http://dx.doi.org/10.1093/nar/gkw1317 |
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