Genomic rearrangements in cancer can join the sequences of two separate genes. Studies of such gene fusion events have mainly focused on identification of fusion proteins from the chimeric transcripts. We have previously investigated how fusions instead can affect the expression of intronic microRNA (miRNA) genes that are encoded within fusion gene partners. Here, we extend our analysis to small nucleolar RNAs (snoRNAs) that also are embedded within protein-coding or noncoding host genes. We found that snoRNA hosts are selectively enriched in fusion transcripts, like miRNA host genes, and that this enrichment is associated with all snoRNA classes. These structural changes may have functional consequences for the cell; proteins involved in the protein translation machinery are overrepresented among snoRNA host genes, a gene architecture assumed to be needed for closely coordinated expression of snoRNAs and host proteins. Our data indicate that this structure is frequently disrupted in cancer. We furthermore observed that snoRNA genes involved in fusions tend to associate with stronger promoters than the natural host, suggesting a mechanism that selects for snoRNA overexpression. In summary, we highlight a previously unexplored frequent structural change in cancer that affects important components of cellular physiology.

中文翻译：

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融合转录本的分析表明，snoRNA及其宿主基因在乳腺癌中广泛失活。

癌症中的基因组重排可以加入两个独立基因的序列。对此类基因融合事件的研究主要集中于从嵌合转录本鉴定融合蛋白。我们以前已经研究过融合如何反而会影响融合基因伴侣中编码的内含子microRNA（miRNA）基因的表达。在这里，我们将分析扩展到还嵌入蛋白质编码或非编码宿主基因中的小核仁RNA（snoRNA）。我们发现snoRNA宿主像miRNA宿主基因一样在融合转录本中选择性富集，并且这种富集与所有snoRNA类有关。这些结构变化可能会对细胞产生功能性影响。参与snoRNA宿主基因的蛋白质翻译机制中涉及的蛋白质过多，snoRNA和宿主蛋白紧密协调表达所需的基因结构。我们的数据表明这种结构在癌症中经常被破坏。我们进一步观察到，参与融合的snoRNA基因倾向于与比天然宿主更强的启动子结合，这提示了选择snoRNA过表达的机制。总而言之，我们重点介绍了影响细胞生理学重要组成部分的癌症之前未曾探索的频繁结构变化。