Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes
Abstract The RNA binding motif X-linked (RBMX) gene plays multiple roles in gene transcription and alternative splicing regulation. Modifications to its expression have been associated with the development of various cancers. In addition to RBMX, there exist several RBMX-like genes (RBMXLs) that hav...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03274-3 |
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| author | Sylvain de Breyne Hélène Polvèche Didier Auboeuf Théophile Ohlmann Henri Gruffat Evelyne Manet |
| author_facet | Sylvain de Breyne Hélène Polvèche Didier Auboeuf Théophile Ohlmann Henri Gruffat Evelyne Manet |
| author_sort | Sylvain de Breyne |
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| description | Abstract The RNA binding motif X-linked (RBMX) gene plays multiple roles in gene transcription and alternative splicing regulation. Modifications to its expression have been associated with the development of various cancers. In addition to RBMX, there exist several RBMX-like genes (RBMXLs) that have been generated by retrotransposition of RBMX. Among these, RBMXL1 encodes a protein that is more than 95% identical to RBMX and may therefore fulfil similar functions. This study identified a specific variation in the alternative splicing of a small exon located in the 5′-untranslated region of the human RBMXL1 mRNA. This occurs following the infection of primary B lymphocytes by the Epstein–Barr virus (EBV) or their activation by a combination of CD40 Ligand and Interleukin 4. The inclusion of this small exon creates a small upstream open reading frame (uORF). Such uORFs have been described as having the capacity to regulate the translation of a downstream ORF. Our findings indicate that the RBMXL1 uORF is functional and that its presence results in the downregulation of the translation of the downstream primary ORF. Regulation of this alternative splicing may therefore play an important role in the fine-tuning of the global level of RBMX/RBMXL1 proteins in the cells. |
| format | Article |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-4f2877ded14443c49fd988c85b4c5ffe2025-08-20T03:03:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-03274-3Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytesSylvain de Breyne0Hélène Polvèche1Didier Auboeuf2Théophile Ohlmann3Henri Gruffat4Evelyne Manet5CIRI, International Center for Infectiology Research, RNA Expression in Viruses and Eukaryotes (REVE) Team, INSERM U1111, CNRS UMR5308, ENS de Lyon, Université Lyon ICECS, I-StemLBMC, Laboratory of Biology and Modelling of the Cell, Regulation of Genome Architecture and Dynamics of Splicing (REGARDS) Team, CNRS UMR 5239, ENS de Lyon, Université Lyon ICIRI, International Center for Infectiology Research, RNA Expression in Viruses and Eukaryotes (REVE) Team, INSERM U1111, CNRS UMR5308, ENS de Lyon, Université Lyon ICIRI, International Center for Infectiology Research, RNA Expression in Viruses and Eukaryotes (REVE) Team, INSERM U1111, CNRS UMR5308, ENS de Lyon, Université Lyon ICIRI, International Center for Infectiology Research, RNA Expression in Viruses and Eukaryotes (REVE) Team, INSERM U1111, CNRS UMR5308, ENS de Lyon, Université Lyon IAbstract The RNA binding motif X-linked (RBMX) gene plays multiple roles in gene transcription and alternative splicing regulation. Modifications to its expression have been associated with the development of various cancers. In addition to RBMX, there exist several RBMX-like genes (RBMXLs) that have been generated by retrotransposition of RBMX. Among these, RBMXL1 encodes a protein that is more than 95% identical to RBMX and may therefore fulfil similar functions. This study identified a specific variation in the alternative splicing of a small exon located in the 5′-untranslated region of the human RBMXL1 mRNA. This occurs following the infection of primary B lymphocytes by the Epstein–Barr virus (EBV) or their activation by a combination of CD40 Ligand and Interleukin 4. The inclusion of this small exon creates a small upstream open reading frame (uORF). Such uORFs have been described as having the capacity to regulate the translation of a downstream ORF. Our findings indicate that the RBMXL1 uORF is functional and that its presence results in the downregulation of the translation of the downstream primary ORF. Regulation of this alternative splicing may therefore play an important role in the fine-tuning of the global level of RBMX/RBMXL1 proteins in the cells.https://doi.org/10.1038/s41598-025-03274-3RBMXL1uORFAlternative splicingTranslational regulationEpstein–Barr virusB lymphocyte activation |
| spellingShingle | Sylvain de Breyne Hélène Polvèche Didier Auboeuf Théophile Ohlmann Henri Gruffat Evelyne Manet Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes Scientific Reports RBMXL1 uORF Alternative splicing Translational regulation Epstein–Barr virus B lymphocyte activation |
| title | Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes |
| title_full | Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes |
| title_fullStr | Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes |
| title_full_unstemmed | Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes |
| title_short | Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes |
| title_sort | alternative splicing in the rbmxl1 5 utr induces uorf mediated translation control in activated b lymphocytes |
| topic | RBMXL1 uORF Alternative splicing Translational regulation Epstein–Barr virus B lymphocyte activation |
| url | https://doi.org/10.1038/s41598-025-03274-3 |
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