Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and has the ability to catalyze the cross-linking of extracellular matrix collagen and elastin. High expression of LOXL2 is related to tumor cell proliferation, invasion, and metastasis. contains 14 exons. Previous studies have found that has abnormal alternative splicing and exon skipping in a variety of tissues and cells, resulting in a new alternatively spliced isoform denoted . lacks exon 13, but its encoded protein has greater ability to induce tumor cell proliferation, invasion, and metastasis. However, the molecular events that produce are still unclear. In this study, we found that overexpression of the splicing factor hnRNPA1 in cells can regulate the alternative splicing of and increase the expression of . The exonic splicing silencer exists at the 3′ splice site and 5′ splice site of exon 13. HnRNPA1 can bind to the exonic splicing silencer and inhibit the inclusion of exon 13. The RRM domain of hnRNPA1 and phosphorylation of hnRNPA1 at S91 and S95 are important for the regulation of alternative splicing. These results show that hnRNPA1 is a splicing factor that enhances the production of .

中文翻译：

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剪接因子 hnRNPA1 调节 LOXL2 的选择性剪接以增强 LOXL2Δ13 的产生


赖氨酰氧化酶样 2 (LOXL2) 是赖氨酰氧化酶家族的一员，具有催化细胞外基质胶原蛋白和弹性蛋白交联的能力。 LOXL2的高表达与肿瘤细胞的增殖、侵袭和转移有关。含有14个外显子。先前的研究发现多种组织和细胞中存在异常的选择性剪接和外显子跳跃，从而产生了一种新的选择性剪接亚型，表示为 。缺乏外显子13，但其编码的蛋白具有更强的诱导肿瘤细胞增殖、侵袭和转移的能力。然而，产生的分子事件仍不清楚。在本研究中，我们发现细胞中剪接因子hnRNPA1的过度表达可以调节 的选择性剪接并增加 的表达。外显子剪接沉默子存在于外显子13的3'剪接位点和5'剪接位点。HnRNPA1可以与外显子剪接沉默子结合并抑制外显子13的包含。hnRNPA1的RRM结构域以及hnRNPA1在S91和S95处的磷酸化是对于选择性剪接的调控很重要。这些结果表明 hnRNPA1 是一种剪接因子，可增强 .