Matrin3 binds directly to intronic pyrimidine-rich sequences and controls alternative splicing
Matrin3 binds directly to intronic pyrimidine-rich sequences and controls alternative splicing
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Matrin3 直接结合富含内含子嘧啶的序列并控制选择性剪接
DOI：
10.1111/gtc.12512
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发表时间：
2017
期刊：
影响因子：
2.1
通讯作者：
Kawahara Y
中科院分区：
文献类型：
--
作者：
Uemura Y;Oshima T;Yamamoto M;Reyes CJ;Costa Cruz PH;Shibuya T;Kawahara Y
Matrin 3是一种RNA结合蛋白，定位于核基质中。虽然已经报道了Matrin 3在RNA代谢中的各种作用，但迄今为止尚未全面研究Matrin 3直接结合的体内靶RNA。在这里，我们发现Matrin 3主要与前mRNA的内含子区域结合。使用人类神经元细胞进行的光活化核糖核苷增强交联和免疫沉淀（PAR-CLIP）分析表明，Matrin 3识别富含嘧啶的序列作为结合基序，包括多聚嘧啶段（一种剪接调控元件）。剪接敏感的微阵列分析显示，Matrin 3的缺失优先增加了与含有Matrin 3结合位点的内含子相邻的盒式外显子的包含。我们进一步发现，尽管大多数被多聚嘧啶束结合蛋白1（PTBP 1）靶向的基因也被Matrin 3结合，但Matrin 3可以以不依赖于PTBP 1的方式控制选择性剪接，至少部分如此。这些发现表明，Matrin 3是一种剪接调节因子，靶向内含子嘧啶丰富的序列。
Matrin3 is an RNA‐binding protein that is localized in the nuclear matrix. Although various roles in RNA metabolism have been reported for Matrin3,in vivotarget RNAs to which Matrin3 binds directly have not been investigated comprehensively so far. Here, we show that Matrin3 binds predominantly to intronic regions of pre‐mRNAs. Photoactivatable Ribonucleoside‐Enhanced Cross‐linking and Immunoprecipitation (PAR‐CLIP) analysis using human neuronal cells showed that Matrin3 recognized pyrimidine‐rich sequences as binding motifs, including the polypyrimidine tract, a splicing regulatory element. Splicing‐sensitive microarray analysis showed that depletion of Matrin3 preferentially increased the inclusion of cassette exons that were adjacent to introns that contained Matrin3‐binding sites. We further found that although most of the genes targeted by polypyrimidine tract binding protein 1 (PTBP1) were also bound by Matrin3, Matrin3 could control alternative splicing in a PTBP1‐independent manner, at least in part. These findings suggest that Matrin3 is a splicing regulator that targets intronic pyrimidine‐rich sequences.