Building Knowledge About Alternatively-spliced Dual-Coding Exons

摘要 人类和其他真核生物中的大多数蛋白质编码基因都由一组外显子组成， 它们连接在一起形成信使RNA(信使RNA)，编码最终的蛋白质 产品。众所周知的选择性剪接现象使单个基因成为可能 通过有条件地只包括基因外显子的一个子集来编码多个蛋白质产品 转化为表达的mRNA.一种更令人惊讶的生产替代蛋白质产品的机制 是通过异常剪接利用标准外显子的替代阅读框架；使用 在我们研究组构建的定制软件中，我们发现这种机制似乎是 这很常见。具体地说，大约13%的人类基因至少包含一个有条件的外显子 编码交替的多肽，这些“双重编码外显子”是高度保守的：98% 对应于小鼠基因组中的同源外显子，也编码两个开放阅读 画框。光探索发现了数十个显示组织特异性的人类基因 阅读框架的使用模式，表明至少这些变体中的一些具有功能作用。 在这里，我们描述了一项计划，以(I)利用大规模的人类组织特异性和 发展特定的RNA-Seq和质谱学数据以表格显示差异的程度 使用这些移帧剪接变体，并(Ii)分析计算预测的 双编码变体的结构和功能影响，以及序列信号的控制 他们。这些分析的结果将被累积，以便在公开和可访问的环境中发布 Web服务。

Abstract Most protein-coding genes in humans and other eukaryotes are made up of a collection of exons, which are concatenated to form the messenger RNA (mRNA) that encodes a final protein product. The well-known phenomenon of alternative splicing makes it possible for a single gene to encode multiple protein products, by conditionally including only a subset of the gene’s exons into the expressed mRNA. A more surprising mechanism for producing alternate protein products is to utilize an alternate reading frame of a standard exon, through aberrant splicing; using custom software built in our research group, we have found that this mechanism appears to be quite common. Specifically, ~13% of all human genes include at least one exon that conditionally encodes alternate peptides, and these “dual-coding exons” are highly-conserved: 98% correspond to homologous exons in the mouse genome that also encode two open reading frames. Light exploration has identified dozens of human genes that show tissue-specific patterns of reading frame usage, suggesting a functional role for at least some of these variants. Here, we describe a plan to (i) leverage massive public atlases of human tissue-specific and development-specific RNA-Seq and mass spectrometry data to tabulate the extent of differential use of these frame-shifted splicing variants, and to (ii) analyze the computationally-predicted structural and functional impact of dual-coding variants, and the sequence signals controlling them. The results of these analyses will be accumulated for release in an open and accessible web service.