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首页> 外文期刊>Cell discovery. >Transcriptome-wide identification of the RNA-binding landscape of the chromatin-associated protein PARP1 reveals functions in RNA biogenesis
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Transcriptome-wide identification of the RNA-binding landscape of the chromatin-associated protein PARP1 reveals functions in RNA biogenesis

机译：整个转录组的染色质相关蛋白PARP1的RNA结合景观的鉴定揭示了RNA生物发生中的功能。

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Recent studies implicate Poly (ADP-ribose) polymerase 1 (PARP1) in alternative splicing regulation, and PARP1 may be an RNA-binding protein. However, detailed knowledge of RNA targets and the RNA-binding region for PARP1 are unknown. Here we report the first global study of PARP1–RNA interactions using PAR–CLIP in HeLa cells. We identified a largely overlapping set of 22?142 PARP1–RNA-binding peaks mapping to mRNAs, with 20?484 sites located in intronic regions. PARP1 preferentially bound RNA containing GC-rich sequences. Using a Bayesian model, we determined positional effects of PARP1 on regulated exon-skipping events: PARP1 binding upstream and downstream of the skipped exons generally promotes exon inclusion, whereas binding within the exon of interest and intronic regions closer to the skipped exon promotes exon skipping. Using truncation mutants, we show that removal of the Zn1Zn2 domain switches PARP1 from a DNA binder to an RNA binder. This study represents a first step into understanding the role of PARP1–RNA interaction. Continued identification and characterization of the functional interplay between PARPs and RNA may provide important insights into the role of PARPs in RNA regulation.
机译：最近的研究表明，聚（ADP-核糖）聚合酶1（PARP1）参与了其他剪接调控，而PARP1可能是一种RNA结合蛋白。但是，有关RNA靶标和PARP1的RNA结合区的详细知识尚不清楚。在这里，我们报道了在HeLa细胞中使用PAR-CLIP进行的PARP1-RNA相互作用的首次全球研究。我们确定了一个映射到mRNA的22？142 PARP1–RNA结合峰的大部分重叠区域，其中20？484个位点位于内含子区域。 PARP1优先结合含有富含GC的序列的RNA。使用贝叶斯模型，我们确定了PARP1对调节的外显子跳跃事件的位置影响：PARP1结合跳跃外显子的上游和下游通常会促进外显子包涵，而感兴趣外显子和更靠近跳跃外显子的内含子区域内的结合会促进外显子跳跃。 。使用截断突变体，我们显示Zn1Zn2域的删除将PARP1从DNA结合物切换到RNA结合物。这项研究代表了了解PARP1-RNA相互作用的第一步。持续鉴定和表征PARPs与RNA之间的功能相互作用可能为PARPs在RNA调节中的作用提供重要的见解。

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