Previously we showed that the germline-specific RNA binding protein RBMXL2 is essential for male meiosis where it represses cryptic splicing patterns. Here we find that its ubiquitously expressed paralog RBMX helps underpin human genome stability by preventing non-productive splicing. In particular, RBMX blocks selection of aberrant splice and polyadenylation sites within some ultra-long exons that would interfere with genes needed for normal replication fork activity. Target exons include within the ETAA1 (Ewings Tumour Associated 1) gene, where RBMX collaborates with its interaction partner Tra2β to enable full-length exon inclusion by blocking selection of an aberrant 3′ splice site. Our data reveal a novel group of RNA processing targets potently repressed by RBMX, and help explain why RBMX is associated with gene expression networks in cancer, replication and sensitivity to genotoxic drugs.

中文翻译：

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RBMX使生产超长外显子的RNA加工对于基因组稳定性至关重要

以前，我们表明种系特异性RNA结合蛋白RBMXL2对于雄性减数分裂至关重要，在该过程中，它抑制了隐密的剪接模式。在这里，我们发现其普遍表达的旁系同源物RBMX通过防止非生产性剪接而有助于增强人类基因组的稳定性。特别是，RBMX会阻止某些超长外显子中异常剪接和聚腺苷酸化位点的选择，这会干扰正常的复制叉活性所需的基因。目标外显子包括在ETAA1（与Ewings肿瘤相关的1）基因，其中RBMX与它的相互作用伙伴Tra2β合作，通过阻止对3'异常剪接位点的选择来使全长外显子包含在内。我们的数据揭示了一组新的RNA处理靶点，其被RBMX强力抑制，并有助于解释为什么RBMX与癌症中的基因表达网络，复制和对遗传毒性药物的敏感性相关。