Abstract

CPEB (Cytoplasmic Polyadenylation Element Binding) proteins are a family of four RNA-binding proteins that regulate the translation of maternal mRNAs controlling meiotic cell cycle progression. But CPEBs are not limited to the transcriptionally silent germline; they are also expressed, in various combinations, in somatic cells, yet their role in regulation of mitosis-related gene expression is largely unknown. Deregulation of CPEB1 and CPEB4 have been linked to tumor development. However, a systematic analysis addressing their requirements for the temporal regulation of mitotic gene expression has yet to be performed. This study addresses the requirements of each of the four CPEBs for mitotic phase transitions, with a particular focus on cytoplasmic polyadenylation and translational regulation. We demonstrate that CPEB3 is the only member dispensable for mitotic cell division, whereas the other three members, CPEB1, 2, and 4, are essential to successful mitotic cell division. Thus, CPEB1 is required for prophase entry, CPEB2 for metaphase and CPEB4 for cytokinesis. These three CPEBs have sequential non-redundant functions that promote the phase-specific polyadenylation and translational activation of CPE-regulated transcripts in the mitotic cell cycle.

Highlights

  • Cytoplasmic changes in poly(A) tail length regulate the translation of mRNAs in many biological contexts [1,2,3,4]

  • We found that CPEB1 is required for prophase entry, CPEB2 for metaphase-to-anaphase transition, and CPEB4 for cytokinesis and proper chromosomal segregation

  • We found that transformed cells of distinct origin, tissue and species, expressed different ratios of CPE-Binding Proteins (CPEBs) mRNAs

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Summary

Introduction

Cytoplasmic changes in poly(A) tail length regulate the translation of mRNAs in many biological contexts [1,2,3,4]. Cytoplasmic poly(A) tail elongation is mediated primarily by a cis-acting element, named the Cytoplasmic Polyadenylation Element (CPE), present in the 3’-UTR of the regulated transcripts. This element is targeted by CPE-Binding Proteins (CPEBs), which have RNA-binding capabilities. CPEBs recognize overlapping mRNA populations, with different affinities, but are differentially regulated through the divergent N-terminal regulatory. CPEBs 1, 2 and 4 Coordinate Cell Cycle Progression

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