脚手架蛋白 AKAP12 调节mRNA局部化和翻译
Madeleine R Smith1, Parisa Naeli2, Seyed M Jafarnejad2
1Wellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast BT9 7BL, United Kingdom.
概括
A-酶基蛋白12 (AKAP12) 将信使RNA (mRNA) 在血上,控制蛋白质的产生. 这种AKAP12介导的mRNA定位对于内皮细胞迁移和血管形成至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 基因表达规范 基因表达规范
背景情况:
- 使者RNA (mRNA) 局部化提供了对基因表达的空间控制.
- 将mRNA结到特定亚细胞位置的蛋白质在很大程度上是未知的.
- 内皮细胞迁移和血管生成涉及精确调节蛋白质合成.
研究的目的:
- 识别在迁移的内皮细胞中将mRNA结到亚细胞域的因素.
- 研究A-酶基蛋白12 (AKAP12) 在mRNA定位和功能中的作用.
- 阐明AKAP12调节阿贝尔森氨酸蛋白激酶2 (ABL2) 的机制. mRNA.
主要方法:
- 在迁移的内皮细胞中进行无偏的RNA结合蛋白质组分析.
- 使用质谱学识别mRNA-蛋白相互作用.
- 功能性测试评估了filopodia形成和血管发芽.
- 在存在或不存在AKAP12的情况下分析mRNA翻译效率.
主要成果:
- AKAP12被确定为一种与各种mRNA相互作用的关键蛋白质,包括编码actin重塑激酶的mRNA.
- AKAP12特别针对的是阿贝尔森氨酸蛋白激酶2 (ABL2) mRNA.
- AKAP12对于将ABL2mRNA固定在血膜上至关重要.
- 丢失AKAP12会降低ABL2mRNA的翻译效率,从而损害了filopodia的形成和血管发芽.
结论:
- AKAP12在调节mRNA局部化和翻译方面具有一种新的转录后功能.
- 通过AKAP12介导的ABL2mRNA到等离子体膜的局部化对于内皮细胞功能至关重要.
- 这项研究揭示了内皮细胞中基因表达的空间控制机制.
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