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Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium
The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482499/ https://www.ncbi.nlm.nih.gov/pubmed/34622152 http://dx.doi.org/10.1016/j.isci.2021.103097 |
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author | Zhang, Xiaoli Wang, Ze Xu, Qing Chen, Yuhan Liu, Wen Zhong, Tong Li, Hongchang Quan, Chengshi Zhang, Lingqiang Cui, Chun-Ping |
author_facet | Zhang, Xiaoli Wang, Ze Xu, Qing Chen, Yuhan Liu, Wen Zhong, Tong Li, Hongchang Quan, Chengshi Zhang, Lingqiang Cui, Chun-Ping |
author_sort | Zhang, Xiaoli |
collection | PubMed |
description | The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here, Srsf5 knockout (Srsf5(−/−)) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased in Srsf5(−/−) mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development. |
format | Online Article Text |
id | pubmed-8482499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84824992021-10-06 Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium Zhang, Xiaoli Wang, Ze Xu, Qing Chen, Yuhan Liu, Wen Zhong, Tong Li, Hongchang Quan, Chengshi Zhang, Lingqiang Cui, Chun-Ping iScience Article The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here, Srsf5 knockout (Srsf5(−/−)) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased in Srsf5(−/−) mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development. Elsevier 2021-09-10 /pmc/articles/PMC8482499/ /pubmed/34622152 http://dx.doi.org/10.1016/j.isci.2021.103097 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Zhang, Xiaoli Wang, Ze Xu, Qing Chen, Yuhan Liu, Wen Zhong, Tong Li, Hongchang Quan, Chengshi Zhang, Lingqiang Cui, Chun-Ping Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
title | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
title_full | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
title_fullStr | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
title_full_unstemmed | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
title_short | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
title_sort | splicing factor srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482499/ https://www.ncbi.nlm.nih.gov/pubmed/34622152 http://dx.doi.org/10.1016/j.isci.2021.103097 |
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