CPEB4 replaces CPEB1 to complete meiosis

Abstract

In vertebrate oocytes, meiotic progression is driven by the sequential translational activation of maternal messenger RNAs stored in the cytoplasm. This activation is mainly induced by the cytoplasmic elongation of their poly(A) tails, which is mediated by the cytoplasmic polyadenylation element (CPE) present in their 3’ untranslated regions (3´ UTRs). Sequential, phase-specific translation of these maternal mRNAs is required to complete the two meiotic divisions. Although the earlier polyadenylation events in prophase I and metaphase I are driven by the CPE-binding protein 1 (CPEB1), 90% of this protein is degraded by the anaphase promoting complex in the first meiotic division. The low levels of CPEB1 during interkinesis and in metaphase II raise the question of how the cytoplasmic polyadenylation required for the second meiotic division is achieved. In this work, we demonstrate that CPEB1 activates the translation of the maternal mRNA encoding CPEB4, which, in turn, recruits the cytoplasmic poly(A) polymerase GLD2 to “late” CPE-regulated mRNAs driving the transition from metaphase I to metaphase II, and, therefore, replacing CPEB1 for “late” meiosis polyadenylation.Programa de doctorat en Biomedicina