biostudies-literatureSiachisumo CKing Fahad Medical CityBiotechnology and Biological Sciences Research CouncilRP89705https://www.ebi.ac.uk/biostudies/studies/S-EPMC11446547biostudies-literatureUnknown12Previously, we showed that the germ cell-specific nuclear protein RBMXL2 represses cryptic splicing patterns during meiosis and is required for male fertility (Ehrmann et al., 2019). Here, we show that in somatic cells the similar yet ubiquitously expressed RBMX protein has similar functions. RBMX regulates a distinct class of exons that exceed the median human exon size. RBMX protein-RNA interactions are enriched within ultra-long exons, particularly within genes involved in genome stability, and repress the selection of cryptic splice sites that would compromise gene function. The <i>RBMX</i> gene is silenced during male meiosis due to sex chromosome inactivation. To test whether RBMXL2 might replace the function of RBMX during meiosis we induced expression of RBMXL2 and the more distanteLifeAn anciently diverged family of RNA binding proteins maintain correct splicing of a class of ultra-long exons through cryptic splice site repression.PMC11446547BB/W002019/1Newcastle Liverpool Durham BBSRC Doctoral Training Partnership (BB/M011186/1)BB/M011186/1BB/S008039/1BB/P006612/1BB/W000172/1Smith GRMunkley JGazzara MRElliott DJLuzzi SBarash YCheung KJames KYonchev IDAldalaqan SKheirollahi Chadegani MHysenaj GEhrmann IEDalgliesh CCockell SJSiachisumo CWilson SAfalseAn anciently diverged family of RNA binding proteins maintain correct splicing of a class of ultra-long exons through cryptic splice site repression.Previously, we showed that the germ cell-specific nuclear protein RBMXL2 represses cryptic splicing patterns during meiosis and is required for male fertility (Ehrmann et al., 2019). Here, we show that in somatic cells the similar yet ubiquitously expressed RBMX protein has similar functions. RBMX regulates a distinct class of exons that exceed the median human exon size. RBMX protein-RNA interactions are enriched within ultra-long exons, particularly within genes involved in genome stability, and repress the selection of cryptic splice sites that would compromise gene function. The <i>RBMX</i> gene is silenced during male meiosis due to sex chromosome inactivation. To test whether RBMXL2 might replace the function of RBMX during meiosis we induced expression of RBMXL2 and the more distant2024-01-01T00:00:00Z2024 Oct2026-07-15T05:09:25.244Z2025-04-04T12:53:48.083ZS-EPMC114465473935610610.7554/eLife.89705