平衡的PABP-RNA枢纽在发育过程中实现了信号依赖的mRNA衰变
Miha Modic1,2,3, Klara Kuret4,5,6, Sebastian Steinhauser4
1The Francis Crick Institute, London, UK. miha.modic@kcl.ac.uk.
Nature structural & molecular biology
|July 25, 2024
概括
细胞外信号调节激酶 (ERK) 和基激活蛋白激酶激酶 (MEK) 信号快速降解天真多能性mRNAs. 这一由LIN28A和多A结合蛋白 (PABP) 调节的过程,可以促进发育的进展.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 基因规则 基因规则
背景情况:
- 细胞命运过渡是由改变基因表达的信号通路驱动的.
- 响应信号的快速和选择性转录组重新连接的机制尚不清楚.
研究的目的:
- 阐明细胞外信号调节激酶 (ERK) - - 线素激活蛋白激酶激酶 (MEK) - - 诱导天真多能mRNAs衰变的机制.
- 为了确定在这种衰变过程中涉及的序列决定因素和跨作用调节剂.
主要方法:
- 深度学习分析以确定序列决定因素和跨作用调节器.
- 研究了LIN28A酸化的作用及其与多A结合蛋白 (PABP) 的相互作用.
主要成果:
- ERK-MEK信号酸盐LIN28A,促进其与PABP在原始多能性mRNA的3'未翻译区域 (3'UTRs) 的相互作用.
- 3'UTR中的AU动图促进了LIN28A-PABP的融合,增强了PABP的结合,促进了mRNA的衰变.
- 这种快速的衰变使得从幼稚的多能性过渡到原始的多能性.
结论:
- 信号诱导的LIN28A和PABP-RNA枢纽的融合驱动了原始mRNA的选择性衰变.
- 这种机制促进了快速的转录组重塑,这对于发育进展至关重要,例如胚胎植入.
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