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首页> 外文期刊>Genome Biology >The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes
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The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes

机译：两种SR蛋白的RNA结合态势揭示了独特的功能并与多种RNA类型结合

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Background: The SR proteins comprise a family of essential, structurally related RNA binding proteins. Thecomplexity of their RNA targets and specificity of RNA recognition in vivo is not well understood. Here we useiCLIP to globally analyze and compare the RNA binding properties of two SR proteins, SRSF3 and SRSF4, in murinecells. Results: SRSF3 and SRSF4 binding sites mapped to largely non-overlapping target genes, and in vivo consensusbinding motifs were distinct. Interactions with intronless and intron-containing mRNAs as well as non-coding RNAswere detected. Surprisingly, both SR proteins bound to the 3’ ends of the majority of intronless histone transcripts,implicating SRSF3 and SRSF4 in histone mRNA metabolism. In contrast, SRSF3 but not SRSF4 specifically boundtranscripts encoding numerous RNA binding proteins. Remarkably, SRSF3 was shown to modulate alternativesplicing of its own as well as three other transcripts encoding SR proteins. These SRSF3-mediated splicing eventsled to downregulation of heterologous SR proteins via nonsense-mediated decay. Conclusions: SRSF3 and SRSF4 display unique RNA binding properties underlying diverse cellular regulatorymechanisms, with shared as well as unique coding and non-coding targets. Importantly, CLIP analysis led to thediscovery that SRSF3 cross-regulates the expression of other SR protein family members.
机译：背景：SR蛋白包含一系列必不可少的，结构相关的RNA结合蛋白。他们的RNA靶标的复杂性和体内RNA识别的特异性尚不清楚。在这里，我们使用iCLIP来全局分析和比较鼠细胞中两种SR蛋白SRSF3和SRSF4的RNA结合特性。结果：SRSF3和SRSF4结合位点映射到很大程度上不重叠的目标基因，并且体内共有结合基序是截然不同的。检测到与无内含子和含内含子的mRNA以及非编码RNA的相互作用。出人意料的是，两种SR蛋白都与大多数无内含子组蛋白转录物的3'末端结合，暗示SRSF3和SRSF4参与组蛋白mRNA代谢。相反，SRSF3但不是SRSF4特异性结合转录本，可编码多种RNA结合蛋白。值得注意的是，SRSF3被证明可调节其自身以及编码SR蛋白的其他三个转录物的选择性剪接。这些SRSF3介导的剪接通过无意义介导的衰变导致异源SR蛋白的下调。结论：SRSF3和SRSF4在不同的细胞调节机制下表现出独特的RNA结合特性，具有共享的以及独特的编码和非编码靶标。重要的是，CLIP分析导致发现SFSF3交叉调节其他SR蛋白家族成员的表达。

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