Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts.
Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts.
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嵌合体形成：由嵌合RNA转录物编码的蛋白质的潜在功能。
DOI：
10.1101/gr.130062.111
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发表时间：
2012-07
期刊：
影响因子：
7
通讯作者：
Valencia A
中科院分区：
文献类型：
--
作者：
Frenkel-Morgenstern M;Lacroix V;Ezkurdia I;Levin Y;Gabashvili A;Prilusky J;Del Pozo A;Tress M;Johnson R;Guigo R;Valencia A
嵌合RNA包含来自两个或更多个不同基因的外显子，并且具有编码改变细胞表型的新型蛋白质的潜力。迄今为止，许多推定的嵌合转录本已被确定在EST中分离自几种生物体和使用高通量RNA测序。已经表征的少数相应蛋白质产物主要由染色体易位引起，并且与癌症相关。在这里，我们系统地建立了一些假定的嵌合转录本在人类细胞中真正表达。利用高通量RNA测序、质谱实验数据和功能注释，我们研究了7424个假定的人类嵌合RNA。我们证实了175种嵌合RNA在16种人体组织中的表达，丰度从0.06到17 RPKM（每千碱基每百万映射读数的读数）不等。我们表明，这些嵌合RNA是显着更组织特异性比非嵌合转录。此外，我们提出的证据表明，嵌合体倾向于纳入高表达的基因。尽管大多数嵌合RNA的表达水平较低，但我们发现12种新的嵌合体被翻译成在多个鸟枪质谱实验中可检测到的蛋白质。此外，我们确认了三个新的嵌合蛋白质的表达，使用靶向质谱。最后，基于我们的外显子组织和保留的结构域的功能注释，我们讨论了嵌合蛋白的潜在功能与说明性的例子，并建议嵌合体显着利用信号肽和跨膜结构域，这可以改变同源蛋白的细胞定位。总之，这些发现确定了一些嵌合RNA在人类中被翻译成潜在的功能蛋白质。
Chimeric RNAs comprise exons from two or more different genes and have the potential to encode novel proteins that alter cellular phenotypes. To date, numerous putative chimeric transcripts have been identified among the ESTs isolated from several organisms and using high throughput RNA sequencing. The few corresponding protein products that have been characterized mostly result from chromosomal translocations and are associated with cancer. Here, we systematically establish that some of the putative chimeric transcripts are genuinely expressed in human cells. Using high throughput RNA sequencing, mass spectrometry experimental data, and functional annotation, we studied 7424 putative human chimeric RNAs. We confirmed the expression of 175 chimeric RNAs in 16 human tissues, with an abundance varying from 0.06 to 17 RPKM (Reads Per Kilobase per Million mapped reads). We show that these chimeric RNAs are significantly more tissue-specific than non-chimeric transcripts. Moreover, we present evidence that chimeras tend to incorporate highly expressed genes. Despite the low expression level of most chimeric RNAs, we show that 12 novel chimeras are translated into proteins detectable in multiple shotgun mass spectrometry experiments. Furthermore, we confirm the expression of three novel chimeric proteins using targeted mass spectrometry. Finally, based on our functional annotation of exon organization and preserved domains, we discuss the potential features of chimeric proteins with illustrative examples and suggest that chimeras significantly exploit signal peptides and transmembrane domains, which can alter the cellular localization of cognate proteins. Taken together, these findings establish that some chimeric RNAs are translated into potentially functional proteins in humans.
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