Mammalian pumilio proteins control cellular morphology, migration, and adhesion.
Mammalian pumilio proteins control cellular morphology, migration, and adhesion.
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DOI：
10.1038/s41598-023-30004-4
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发表时间：
2023-02-21
影响因子：
4.6
通讯作者：
Karginov, Fedor V. V.
中科院分区：
文献类型：
--
作者：
Sternburg, Erin L. L.;Lillibridge, Jordan J. J.;Phandthong, Rattapol;Karginov, Fedor V. V.
Pumilio蛋白是RNA结合蛋白，其通过结合靶mRNA的3' UTR来控制mRNA翻译和稳定性。哺乳动物有两种典型的Pumilio蛋白，Pumilio 1和Pumilio 2，已知它们在许多生物过程中起作用，包括胚胎发育、神经发生、细胞周期调节和基因组稳定性。在这里，我们的特点是一个新的作用，除了以前已知的缺陷，在T-REx-293细胞中的细胞形态，迁移和粘附，在生长速度的调节bp 1和bp 2。PUM双敲除（PDKO）细胞的细胞组分和生物过程中的差异表达基因的基因本体论分析显示富集在粘附和迁移相关的类别。PDKO细胞的集体细胞迁移率显著低于WT细胞，并显示肌动蛋白形态的变化。此外，在生长过程中，PDKO细胞由于不能逃避细胞-细胞接触而聚集成簇（团块）。细胞外基质（Matrigel）的添加减轻了凝集表型。胶原蛋白IV（ColIV），基质胶的主要组分，被证明是允许PDKO细胞适当地单层化的驱动力，然而，ColIV蛋白水平在PDKO细胞中保持不受干扰。本研究描述了一种与细胞形态、迁移和粘附相关的新型细胞表型，这有助于开发更好的PUM在发育过程和疾病中的功能模型。
Pumilio proteins are RNA-binding proteins that control mRNA translation and stability by binding to the 3’ UTR of target mRNAs. Mammals have two canonical Pumilio proteins, PUM1 and PUM2, which are known to act in many biological processes, including embryonic development, neurogenesis, cell cycle regulation and genomic stability. Here, we characterized a new role of both PUM1 and PUM2 in regulating cell morphology, migration, and adhesion in T-REx-293 cells, in addition to previously known defects in growth rate. Gene ontology analysis of differentially expressed genes in PUM double knockout (PDKO) cells for both cellular component and biological process showed enrichment in categories related to adhesion and migration. PDKO cells had a collective cell migration rate significantly lower than that of WT cells and displayed changes in actin morphology. In addition, during growth, PDKO cells aggregated into clusters (clumps) due to an inability to escape cell–cell contacts. Addition of extracellular matrix (Matrigel) alleviated the clumping phenotype. Collagen IV (ColIV), a major component of Matrigel, was shown to be the driving force in allowing PDKO cells to monolayer appropriately, however, ColIV protein levels remained unperturbed in PDKO cells. This study characterizes a novel cellular phenotype associated with cellular morphology, migration, and adhesion which can aid in developing better models for PUM function in both developmental processes and disease.
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影响因子：
4
作者：
Daley, William P.;Yamada, Kenneth M.
通讯作者：
Yamada, Kenneth M.
影响因子：
11.8
作者：
Carreira-Rosario A;Bhargava V;Hillebrand J;Kollipara RK;Ramaswami M;Buszczak M
通讯作者：
Buszczak M
影响因子：
9.2
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影响因子：
64.5
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通讯作者：
Tuschl T
影响因子：
5.7
作者：
Lu, Gang;Hall, Traci M. Tanaka
通讯作者：
Hall, Traci M. Tanaka