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.

We identified a mechanism of VEGF overexpression in liver and mesentery that promotes pathologic, but not physiologic, angiogenesis, via sequential and nonredundant functions of CPEB1 and CPEB4. Regulation of CPEB4 by CPEB1 and the CPEB4 autoamplification loop induces pathologic angiogenesis. Strategies to block the activities of CPEBs might be developed to treat chronic liver and other angiogenesis-dependent diseases.

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