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Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells
Developmental Cell ( IF 11.8 ) Pub Date : 2020-11-09 , DOI: 10.1016/j.devcel.2020.10.006
Maria Dermit 1 , Martin Dodel 1 , Flora C Y Lee 2 , Muhammad S Azman 1 , Hagen Schwenzer 3 , J Louise Jones 4 , Sarah P Blagden 3 , Jernej Ule 2 , Faraz K Mardakheh 1
Affiliation  

Translation of ribosomal protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms that modulate RP-mRNA translation in coordination with other cellular processes are poorly defined. Here, we show that subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to the actin-rich cell protrusions. This localization is mediated by La-related protein 6 (LARP6), an RNA-binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, enhancing RP synthesis, ribosome biogenesis, and the overall protein synthesis in migratory cells. In human breast carcinomas, epithelial-to-mesenchymal transition (EMT) upregulates LARP6 expression to enhance protein synthesis and support invasive growth. Our findings reveal LARP6-mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration and demonstrate a role for this process in cancer progression downstream of EMT.



中文翻译:

亚细胞 mRNA 定位调节迁移细胞中的核糖体生物发生

核糖体蛋白编码 mRNA (RP-mRNA) 的翻译构成核糖体生物发生的关键步骤,但与其他细胞过程协调调节 RP-mRNA 翻译的机制尚不清楚。在这里,我们表明 RP-mRNA 的亚细胞定位在细胞迁移过程中充当其翻译的关键调节器。当细胞迁移到周围环境时,RP-mRNA 定位于富含肌动蛋白的细胞突起。这种定位是由 La 相关蛋白 6 (LARP6) 介导的,这是一种富含突起的 RNA 结合蛋白。突起充当 RP-mRNA 的翻译热点,增强 RP 合成、核糖体生物发生和迁移细胞中的整体蛋白质合成。在人类乳腺癌中,上皮间质转化 (EMT) 上调 LARP6 表达以增强蛋白质合成并支持侵袭性生长。我们的研究结果揭示了 LARP6 介导的 mRNA 定位是细胞迁移过程中核糖体生物发生的关键调节因子,并证明了该过程在 EMT 下游癌症进展中的作用。

更新日期:2020-11-09
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