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Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins
Many nascent long non-coding RNAs (lncRNAs) undergo the same maturation steps as pre-mRNAs of protein-coding genes (PCGs), but they are often poorly spliced. To identify the underlying mechanisms for this phenomenon, we searched for putative splicing inhibitory sequences using the ncRNA-a2 as a mode...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344860/ https://www.ncbi.nlm.nih.gov/pubmed/30445574 http://dx.doi.org/10.1093/nar/gky1147 |
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author | Krchňáková, Zuzana Thakur, Prasoon Kumar Krausová, Michaela Bieberstein, Nicole Haberman, Nejc Müller-McNicoll, Michaela Staněk, David |
author_facet | Krchňáková, Zuzana Thakur, Prasoon Kumar Krausová, Michaela Bieberstein, Nicole Haberman, Nejc Müller-McNicoll, Michaela Staněk, David |
author_sort | Krchňáková, Zuzana |
collection | PubMed |
description | Many nascent long non-coding RNAs (lncRNAs) undergo the same maturation steps as pre-mRNAs of protein-coding genes (PCGs), but they are often poorly spliced. To identify the underlying mechanisms for this phenomenon, we searched for putative splicing inhibitory sequences using the ncRNA-a2 as a model. Genome-wide analyses of intergenic lncRNAs (lincRNAs) revealed that lincRNA splicing efficiency positively correlates with 5′ss strength while no such correlation was identified for PCGs. In addition, efficiently spliced lincRNAs have higher thymidine content in the polypyrimidine tract (PPT) compared to efficiently spliced PCGs. Using model lincRNAs, we provide experimental evidence that strengthening the 5′ss and increasing the T content in PPT significantly enhances lincRNA splicing. We further showed that lincRNA exons contain less putative binding sites for SR proteins. To map binding of SR proteins to lincRNAs, we performed iCLIP with SRSF2, SRSF5 and SRSF6 and analyzed eCLIP data for SRSF1, SRSF7 and SRSF9. All examined SR proteins bind lincRNA exons to a much lower extent than expression-matched PCGs. We propose that lincRNAs lack the cooperative interaction network that enhances splicing, which renders their splicing outcome more dependent on the optimality of splice sites. |
format | Online Article Text |
id | pubmed-6344860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63448602019-01-29 Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins Krchňáková, Zuzana Thakur, Prasoon Kumar Krausová, Michaela Bieberstein, Nicole Haberman, Nejc Müller-McNicoll, Michaela Staněk, David Nucleic Acids Res RNA and RNA-protein complexes Many nascent long non-coding RNAs (lncRNAs) undergo the same maturation steps as pre-mRNAs of protein-coding genes (PCGs), but they are often poorly spliced. To identify the underlying mechanisms for this phenomenon, we searched for putative splicing inhibitory sequences using the ncRNA-a2 as a model. Genome-wide analyses of intergenic lncRNAs (lincRNAs) revealed that lincRNA splicing efficiency positively correlates with 5′ss strength while no such correlation was identified for PCGs. In addition, efficiently spliced lincRNAs have higher thymidine content in the polypyrimidine tract (PPT) compared to efficiently spliced PCGs. Using model lincRNAs, we provide experimental evidence that strengthening the 5′ss and increasing the T content in PPT significantly enhances lincRNA splicing. We further showed that lincRNA exons contain less putative binding sites for SR proteins. To map binding of SR proteins to lincRNAs, we performed iCLIP with SRSF2, SRSF5 and SRSF6 and analyzed eCLIP data for SRSF1, SRSF7 and SRSF9. All examined SR proteins bind lincRNA exons to a much lower extent than expression-matched PCGs. We propose that lincRNAs lack the cooperative interaction network that enhances splicing, which renders their splicing outcome more dependent on the optimality of splice sites. Oxford University Press 2019-01-25 2018-11-16 /pmc/articles/PMC6344860/ /pubmed/30445574 http://dx.doi.org/10.1093/nar/gky1147 Text en © The Author(s) 2018. 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 Non-Commercial 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 and RNA-protein complexes Krchňáková, Zuzana Thakur, Prasoon Kumar Krausová, Michaela Bieberstein, Nicole Haberman, Nejc Müller-McNicoll, Michaela Staněk, David Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins |
title | Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins |
title_full | Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins |
title_fullStr | Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins |
title_full_unstemmed | Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins |
title_short | Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with SR proteins |
title_sort | splicing of long non-coding rnas primarily depends on polypyrimidine tract and 5′ splice-site sequences due to weak interactions with sr proteins |
topic | RNA and RNA-protein complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344860/ https://www.ncbi.nlm.nih.gov/pubmed/30445574 http://dx.doi.org/10.1093/nar/gky1147 |
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