Alternative splicing in the RBMXL1 5′-UTR induces uORF-mediated translation control in activated B lymphocytes

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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Bibliographic Details
Main Authors: Sylvain de Breyne, Hélène Polvèche, Didier Auboeuf, Théophile Ohlmann, Henri Gruffat, Evelyne Manet
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
RBMXL1
uORF
Alternative splicing
Translational regulation
Epstein–Barr virus
B lymphocyte activation
Online Access:https://doi.org/10.1038/s41598-025-03274-3
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Summary: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.
ISSN:2045-2322

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