RBMX enables productive RNA processing of ultra-long exons important for genome stability
RBMX enables productive RNA processing of ultra-long exons important for genome stability
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DOI：
10.1101/2020.10.09.333039
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发表时间：
2020-10
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通讯作者：
Sara Luzzi;Gerald Hysenaj;Chileleko Siachisumo;K. Cheung;Matthew R. Gazzara;Katherine James;Caroline Dalgliesh;M. Chadegani;Ingrid Ehrmann;Graham R. Smith;S. Cockell;J. Munkley;Yoseph Barash;D. Elliott
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作者：
Sara Luzzi;Gerald Hysenaj;Chileleko Siachisumo;K. Cheung;Matthew R. Gazzara;Katherine James;Caroline Dalgliesh;M. Chadegani;Ingrid Ehrmann;Graham R. Smith;S. Cockell;J. Munkley;Yoseph Barash;D. Elliott
以前，我们证明了生殖系特异的RNA结合蛋白RBMXL2对于雄性减数分裂是必不可少的，在那里它抑制隐蔽的剪接模式(1)。在这里，我们发现它普遍表达的并行RBMX通过防止非生产性剪接来帮助巩固人类基因组的稳定性。特别是，RBMX阻止了一些超长外显子内异常剪接和多腺苷基化位点的选择，这些外显子将干扰正常复制分叉活动所需的基因。目标外显子包括在ETA1(羽翼肿瘤相关1)基因内，其中RBMX与其相互作用伙伴TRA2β合作，通过阻止选择异常的3‘剪接位点来实现全长外显子的包含。我们的数据揭示了一组新的被RBMX有效抑制的RNA加工靶点，并有助于解释为什么RBMX与癌症、复制和对遗传毒性药物的敏感性的基因表达网络有关。
Previously we showed that the germline-specific RNA binding protein RBMXL2 is essential for male meiosis where it represses cryptic splicing patterns (1). 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.