Conservation of an RNA regulatory map between Drosophila and mammals
Conservation of an RNA regulatory map between Drosophila and mammals
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DOI：
10.1101/gr.108662.110
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发表时间：
2011-02-01
期刊：
影响因子：
7
通讯作者：
Graveley, Brenton R.
中科院分区：
文献类型：
--
作者：
Brooks, Angela N.;Yang, Li;Graveley, Brenton R.
选择性剪接通常由蛋白质控制，所述蛋白质直接结合至调控序列元件并且激活或抑制靶前mRNA中相邻剪接位点的剪接。在这里，我们结合了RNAi和mRNA-seq来鉴定受Pasilla（PS）调控的外显子，Pasilla是哺乳动物NOVA 1和NOVA 2的果蝇直系同源物。我们确定了323个基因中的405个剪接事件，这些基因在PS耗尽后受到显著影响，其中许多被注释为组成性剪接。序列区域上游和PS-阻遏外显子内和PS-激活外显子下游富含YCAY重复序列，这些序列区域与哺乳动物中NOVA调节外显子附近的这些基序的位置一致。因此，PS和NOVA 1/2的RNA调控图谱在昆虫和哺乳动物之间是高度保守的，尽管由PS和NOVA 1/2调控的靶基因直系同源物几乎完全不重叠。这一观察结果表明，个别RNA结合蛋白的调控代码可能是几乎不变的，但这些蛋白质控制的调控模块是高度进化的。
Alternative splicing is generally controlled by proteins that bind directly to regulatory sequence elements and either activate or repress splicing of adjacent splice sites in a target pre-mRNA. Here, we have combined RNAi and mRNA-seq to identify exons that are regulated by Pasilla (PS), the Drosophila melanogaster ortholog of mammalian NOVA1 and NOVA2. We identified 405 splicing events in 323 genes that are significantly affected upon depletion of ps, many of which were annotated as being constitutively spliced. The sequence regions upstream and within PS-repressed exons and downstream from PS-activated exons are enriched for YCAY repeats, and these are consistent with the location of these motifs near NOVA-regulated exons in mammals. Thus, the RNA regulatory map of PS and NOVA1/2 is highly conserved between insects and mammals despite the fact that the target gene orthologs regulated by PS and NOVA1/2 are almost entirely nonoverlapping. This observation suggests that the regulatory codes of individual RNA binding proteins may be nearly immutable, yet the regulatory modules controlled by these proteins are highly evolvable.