Gene Regulation Program, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
Nat Cell Biol. 2010 May;12(5):447-56. doi: 10.1038/ncb2046. Epub 2010 Apr 4.
Meiotic and early-embryonic cell divisions in vertebrates take place in the absence of transcription and rely on the translational regulation of stored maternal messenger RNAs. Most of these mRNAs are regulated by the cytoplasmic-polyadenylation-element-binding protein (CPEB), which mediates translational activation and repression through cytoplasmic changes in their poly(A) tail length. It was unknown whether translational regulation by cytoplasmic polyadenylation and CPEB can also regulate mRNAs at specific points of mitotic cell-cycle divisions. Here we show that CPEB-mediated post-transcriptional regulation by phase-specific changes in poly(A) tail length is required for cell proliferation and specifically for entry into M phase in mitotically dividing cells. This translational control is mediated by two members of the CPEB family of proteins, CPEB1 and CPEB4. We conclude that regulation of poly(A) tail length is not only required to compensate for the lack of transcription in specialized cell divisions but also acts as a general mechanism to control mitosis.
脊椎动物的减数分裂和早期胚胎细胞分裂是在没有转录的情况下进行的,依赖于储存的母体信使 RNA 的翻译调控。这些 mRNA 中的大多数受细胞质多聚腺苷酸化元件结合蛋白 (CPEB) 调控,该蛋白通过其多聚 (A) 尾长的细胞质变化介导翻译激活和抑制。尚不清楚细胞质多聚腺苷酸化和 CPEB 的翻译调控是否也可以调节有丝分裂细胞周期分裂的特定点的 mRNA。在这里,我们表明,CPEB 介导的通过多聚 (A) 尾长的特定变化进行的转录后调控对于细胞增殖,特别是对于有丝分裂细胞进入 M 期是必需的。这种翻译控制是由 CPEB 家族的两个蛋白,CPEB1 和 CPEB4 介导的。我们得出结论,调节多聚 (A) 尾长不仅是专门的细胞分裂中补偿缺乏转录所必需的,而且还作为控制有丝分裂的一般机制。