A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response
Abstract p53-mediated cell cycle arrest during DNA damage is dependent on the induction of p21 protein, encoded by the CDKN1A gene. p21 inhibits cyclin-dependent kinases required for cell cycle progression to guarantee accurate repair of DNA lesions. Hence, fine-tuning of p21 levels is crucial to pr...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43495-6 |
| _version_ | 1797452101074288640 |
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| author | Bella M. Ben-Oz Feras E. Machour Marian Nicola Amir Argoetti Galia Polyak Rawad Hanna Oded Kleifeld Yael Mandel-Gutfreund Nabieh Ayoub |
| author_facet | Bella M. Ben-Oz Feras E. Machour Marian Nicola Amir Argoetti Galia Polyak Rawad Hanna Oded Kleifeld Yael Mandel-Gutfreund Nabieh Ayoub |
| author_sort | Bella M. Ben-Oz |
| collection | DOAJ |
| description | Abstract p53-mediated cell cycle arrest during DNA damage is dependent on the induction of p21 protein, encoded by the CDKN1A gene. p21 inhibits cyclin-dependent kinases required for cell cycle progression to guarantee accurate repair of DNA lesions. Hence, fine-tuning of p21 levels is crucial to preserve genomic stability. Currently, the multilayered regulation of p21 levels during DNA damage is not fully understood. Herein, we identify the human RNA binding motif protein 42 (RBM42) as a regulator of p21 levels during DNA damage. Genome-wide transcriptome and interactome analysis reveals that RBM42 alters the expression of p53-regulated genes during DNA damage. Specifically, we demonstrate that RBM42 facilitates CDKN1A splicing by counteracting the splicing inhibitory effect of RBM4 protein. Unexpectedly, we also show that RBM42, underpins translation of various splicing targets, including CDKN1A. Concordantly, transcriptome-wide mapping of RBM42-RNA interactions using eCLIP further substantiates the dual function of RBM42 in regulating splicing and translation of its target genes, including CDKN1A. Collectively, our data show that RBM42 couples splicing and translation machineries to fine-tune gene expression during DNA damage response. |
| first_indexed | 2024-03-09T15:03:54Z |
| format | Article |
| id | doaj.art-5d2786df41464164a9f134fb00067f8c |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T15:03:54Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-5d2786df41464164a9f134fb00067f8c2023-11-26T13:46:07ZengNature PortfolioNature Communications2041-17232023-11-0114111810.1038/s41467-023-43495-6A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage responseBella M. Ben-Oz0Feras E. Machour1Marian Nicola2Amir Argoetti3Galia Polyak4Rawad Hanna5Oded Kleifeld6Yael Mandel-Gutfreund7Nabieh Ayoub8Department of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyDepartment of Biology, Technion - Israel Institute of TechnologyAbstract p53-mediated cell cycle arrest during DNA damage is dependent on the induction of p21 protein, encoded by the CDKN1A gene. p21 inhibits cyclin-dependent kinases required for cell cycle progression to guarantee accurate repair of DNA lesions. Hence, fine-tuning of p21 levels is crucial to preserve genomic stability. Currently, the multilayered regulation of p21 levels during DNA damage is not fully understood. Herein, we identify the human RNA binding motif protein 42 (RBM42) as a regulator of p21 levels during DNA damage. Genome-wide transcriptome and interactome analysis reveals that RBM42 alters the expression of p53-regulated genes during DNA damage. Specifically, we demonstrate that RBM42 facilitates CDKN1A splicing by counteracting the splicing inhibitory effect of RBM4 protein. Unexpectedly, we also show that RBM42, underpins translation of various splicing targets, including CDKN1A. Concordantly, transcriptome-wide mapping of RBM42-RNA interactions using eCLIP further substantiates the dual function of RBM42 in regulating splicing and translation of its target genes, including CDKN1A. Collectively, our data show that RBM42 couples splicing and translation machineries to fine-tune gene expression during DNA damage response.https://doi.org/10.1038/s41467-023-43495-6 |
| spellingShingle | Bella M. Ben-Oz Feras E. Machour Marian Nicola Amir Argoetti Galia Polyak Rawad Hanna Oded Kleifeld Yael Mandel-Gutfreund Nabieh Ayoub A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response Nature Communications |
| title | A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response |
| title_full | A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response |
| title_fullStr | A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response |
| title_full_unstemmed | A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response |
| title_short | A dual role of RBM42 in modulating splicing and translation of CDKN1A/p21 during DNA damage response |
| title_sort | dual role of rbm42 in modulating splicing and translation of cdkn1a p21 during dna damage response |
| url | https://doi.org/10.1038/s41467-023-43495-6 |
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