Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells.
Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells.
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DOI：
10.1016/j.devcel.2020.10.006
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发表时间：
2020-11-09
影响因子：
11.8
通讯作者：
Mardakheh FK
中科院分区：
文献类型：
--
作者：
Dermit M;Dodel M;Lee FCY;Azman MS;Schwenzer H;Jones JL;Blagden SP;Ule J;Mardakheh FK
核糖体蛋白编码mRNA（RP - mRNA）的翻译是核糖体生物发生的关键步骤，但与其他细胞过程协同调节RP - mRNA翻译的机制尚不明确。在此，我们表明在细胞迁移过程中，RP - mRNA的亚细胞定位是其翻译的关键调节因素。当细胞迁移至周围环境时，RP - mRNA定位于富含肌动蛋白的细胞突起处。这种定位是由La相关蛋白6（LARP6）介导的，LARP6是一种富集于突起处的RNA结合蛋白。突起作为RP - mRNA翻译的热点，增强了核糖体蛋白合成、核糖体生物发生以及迁移细胞中的整体蛋白质合成。在人乳腺癌中，上皮 - 间质转化（EMT）上调LARP6的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素，并证明了这一过程在EMT下游的癌症进展中发挥作用。
RP - mRNA的翻译是核糖体生物发生的关键步骤
在迁移细胞中，LARP6将RP - mRNA定位于富含肌动蛋白的细胞突起
突起作为RP - mRNA翻译的热点，增强核糖体生物发生
LARP6的表达与EMT相关，在侵袭性癌中上调
德尔米特等人揭示核糖体蛋白（RP）- mRNA定位于迁移细胞的突起前沿，在那里它们的翻译局部增加，导致核糖体生物发生和蛋白质合成上调。在侵袭性癌中，该途径上调以支持侵袭性癌细胞的高合成代谢需求。
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. Translation of RP-mRNAs is a key step in ribosome biogenesis In migrating cells, LARP6 localizes RP-mRNAs to actin-rich cell protrusions Protrusions act as hotspots of RP-mRNA translation, enhancing ribosome biogenesis LARP6 expression is associated with EMT and upregulated in aggressive carcinomas Dermit et al. reveal that ribosomal protein (RP)-mRNAs localize to the protrusive fronts of migratory cells, where their translation is locally increased, leading to upregulation of ribosome biogenesis and protein synthesis. In aggressive carcinomas, this pathway is upregulated in order to support the high anabolic demands of invasive cancer cells.
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影响因子：
4.8
作者：
Huppertz, Ina;Attig, Jan;D'Ambrogio, Andrea;Easton, Laura E.;Sibley, Christopher R.;Sugimoto, Yoichiro;Tajnik, Mojca;Koenig, Julian;Ule, Jernej
通讯作者：
Ule, Jernej
影响因子：
9.2
作者：
Lam, Yun Wah;Lamond, Angus I.;Mann, Matthias;Andersen, Jens S.
通讯作者：
Andersen, Jens S.
影响因子：
7.7
作者：
Lahr, Roni M.;Fonseca, Bruno D.;Berman, Andrea J.
通讯作者：
Berman, Andrea J.
影响因子：
8.8
作者：
Lawrence RT;Perez EM;Hernández D;Miller CP;Haas KM;Irie HY;Lee SI;Blau CA;Villén J
通讯作者：
Villén J
DOI：
10.1083/jcb.201002102
发表时间：
2010-04-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Karbstein K
通讯作者：
Karbstein K