Boraas Liana C, Hu Mengwei, Martino Pieter, Thornton Lauren, Vejnar Charles E, Zhen Gang, Zeng Longhui, Parker Dylan M, Cox Andy L, Giraldez Antonio J, Su Xiaolei, Mayr Christine, Wang Siyuan, Nicoli Stefania
Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Cell Rep. 2025 Feb 25;44(2):115237. doi: 10.1016/j.celrep.2025.115237. Epub 2025 Feb 1.
The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration. For instance, β-actin mRNA and its associated RNA-binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs) to support localized β-actin synthesis, crucial for cell migration. However, whether other mRNAs and RBPs also localize at FAs remains unclear. Here, we identify hundreds of mRNAs that are enriched at FAs (FA-mRNAs). FA-mRNAs share characteristics with stress granule (SG) mRNAs and are found in ribonucleoprotein (RNP) complexes with the SG RBP. Mechanistically, G3BP1 binds to FA proteins in an RNA-dependent manner, and its RNA-binding and dimerization domains, essential for G3BP1 to form RNPs in SG, are required for FA localization and cell migration. We find that G3BP1 RNPs promote cell speed by enhancing FA protein mobility and FA size. These findings suggest a previously unappreciated role for G3BP1 RNPs in regulating FA function under non-stress conditions.
mRNA的亚细胞定位在包括细胞迁移在内的生物过程中起着关键作用。例如，β-肌动蛋白mRNA及其相关的RNA结合蛋白（RBP），即ZBP1/IGF2BP1，被募集到粘着斑（FAs）以支持局部β-肌动蛋白的合成，这对细胞迁移至关重要。然而，其他mRNA和RBP是否也定位于粘着斑仍不清楚。在这里，我们鉴定出数百种在粘着斑富集的mRNA（粘着斑mRNA）。粘着斑mRNA与应激颗粒（SG）mRNA具有共同特征，并存在于与SG RBP形成的核糖核蛋白（RNP）复合物中。从机制上讲，G3BP1以RNA依赖的方式与粘着斑蛋白结合，其RNA结合和二聚化结构域是G3BP1在应激颗粒中形成RNP所必需的，也是粘着斑定位和细胞迁移所必需的。我们发现G3BP1 RNP通过增强粘着斑蛋白的流动性和粘着斑大小来提高细胞速度。这些发现表明，G3BP1 RNP在非应激条件下调节粘着斑功能方面具有以前未被认识到的作用。
