Rbm3 deficiency leads to transcriptome-wide splicing alterations
Rbm3 (RNA-binding motif protein 3) is a stress responsive gene, which maintains cellular homeostasis and promotes survival upon various harmful cellular stimuli. Rbm3 protein shows conserved structural and molecular similarities to heterogeneous nuclear ribonucleoproteins (hnRNPs), which regulate al...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | RNA Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2024.2413820 |
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| _version_ | 1850105674110861312 |
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| author | Steffen Erkelenz Marta Grzonka Antonios Papadakis Heiner Schaal Jan H. J. Hoeijmakers Ákos Gyenis |
| author_facet | Steffen Erkelenz Marta Grzonka Antonios Papadakis Heiner Schaal Jan H. J. Hoeijmakers Ákos Gyenis |
| author_sort | Steffen Erkelenz |
| collection | DOAJ |
| description | Rbm3 (RNA-binding motif protein 3) is a stress responsive gene, which maintains cellular homeostasis and promotes survival upon various harmful cellular stimuli. Rbm3 protein shows conserved structural and molecular similarities to heterogeneous nuclear ribonucleoproteins (hnRNPs), which regulate all steps of the mRNA metabolism. Growing evidence is pointing towards a broader role of Rbm3 in various steps of gene expression. Here, we demonstrate that Rbm3 deficiency is linked to transcriptome-wide pre-mRNA splicing alterations, which can be reversed through Rbm3 co-expression from a cDNA. Using an MS2 tethering assay, we show that Rbm3 regulates splice site selection similar to other hnRNP proteins when recruited between two competing 5[Formula: see text] splice sites. Furthermore, we show that the N-terminal part of Rbm3 encompassing the RNA recognition motif (RRM), is sufficient to elicit changes in splice site selection. On the basis of these findings, we propose a novel, undescribed function of Rbm3 in RNA splicing that contributes to the preservation of transcriptome integrity. |
| format | Article |
| id | doaj-art-b7fdbcb105a146a39dbe9107f8d6a92e |
| institution | OA Journals |
| issn | 1547-6286 1555-8584 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | RNA Biology |
| spelling | doaj-art-b7fdbcb105a146a39dbe9107f8d6a92e2025-08-20T02:39:01ZengTaylor & Francis GroupRNA Biology1547-62861555-85842024-12-012111077108910.1080/15476286.2024.2413820Rbm3 deficiency leads to transcriptome-wide splicing alterationsSteffen Erkelenz0Marta Grzonka1Antonios Papadakis2Heiner Schaal3Jan H. J. Hoeijmakers4Ákos Gyenis5Faculty of Medicine, University of Cologne, Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, Köln, GermanyFaculty of Medicine, University of Cologne, Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, Köln, GermanyFaculty of Medicine, University of Cologne, Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, Köln, GermanyInstitute of Virology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyFaculty of Medicine, University of Cologne, Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, Köln, GermanyFaculty of Medicine, University of Cologne, Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, Köln, GermanyRbm3 (RNA-binding motif protein 3) is a stress responsive gene, which maintains cellular homeostasis and promotes survival upon various harmful cellular stimuli. Rbm3 protein shows conserved structural and molecular similarities to heterogeneous nuclear ribonucleoproteins (hnRNPs), which regulate all steps of the mRNA metabolism. Growing evidence is pointing towards a broader role of Rbm3 in various steps of gene expression. Here, we demonstrate that Rbm3 deficiency is linked to transcriptome-wide pre-mRNA splicing alterations, which can be reversed through Rbm3 co-expression from a cDNA. Using an MS2 tethering assay, we show that Rbm3 regulates splice site selection similar to other hnRNP proteins when recruited between two competing 5[Formula: see text] splice sites. Furthermore, we show that the N-terminal part of Rbm3 encompassing the RNA recognition motif (RRM), is sufficient to elicit changes in splice site selection. On the basis of these findings, we propose a novel, undescribed function of Rbm3 in RNA splicing that contributes to the preservation of transcriptome integrity.https://www.tandfonline.com/doi/10.1080/15476286.2024.2413820Rbm3splicingtranscriptional fidelityisoform switchRNA-seq |
| spellingShingle | Steffen Erkelenz Marta Grzonka Antonios Papadakis Heiner Schaal Jan H. J. Hoeijmakers Ákos Gyenis Rbm3 deficiency leads to transcriptome-wide splicing alterations RNA Biology Rbm3 splicing transcriptional fidelity isoform switch RNA-seq |
| title | Rbm3 deficiency leads to transcriptome-wide splicing alterations |
| title_full | Rbm3 deficiency leads to transcriptome-wide splicing alterations |
| title_fullStr | Rbm3 deficiency leads to transcriptome-wide splicing alterations |
| title_full_unstemmed | Rbm3 deficiency leads to transcriptome-wide splicing alterations |
| title_short | Rbm3 deficiency leads to transcriptome-wide splicing alterations |
| title_sort | rbm3 deficiency leads to transcriptome wide splicing alterations |
| topic | Rbm3 splicing transcriptional fidelity isoform switch RNA-seq |
| url | https://www.tandfonline.com/doi/10.1080/15476286.2024.2413820 |
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