Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
EMBO J. 2010 Jan 20;29(2):387-97. doi: 10.1038/emboj.2009.337. Epub 2009 Dec 3.
Meiotic cell-cycle progression in progesterone-stimulated Xenopus oocytes requires that the translation of pre-existing maternal mRNAs occur in a strict temporal order. Timing of translation is regulated through elements within the mRNA 3' untranslated region (3' UTR), which respond to cell cycle-dependant signalling. One element that has been previously implicated in the temporal control of mRNA translation is the cytoplasmic polyadenylation element (CPE). In this study, we show that the CPE does not direct early mRNA translation. Rather, early translation is directed through specific early factors, including the Musashi-binding element (MBE) and the MBE-binding protein, Musashi. Our findings indicate that although the cyclin B5 3' UTR contains both CPEs and an MBE, the MBE is the critical regulator of early translation. The cyclin B2 3' UTR contains CPEs, but lacks an MBE and is translationally activated late in maturation. Finally, utilizing antisense oligonucleotides to attenuate endogenous Musashi synthesis, we show that Musashi is critical for the initiation of early class mRNA translation and for the subsequent activation of CPE-dependant mRNA translation.
在孕酮刺激的爪蟾卵母细胞中,减数分裂细胞周期的进展需要以严格的时间顺序进行先前存在的母体 mRNA 的翻译。翻译的时间由 mRNA 3'非翻译区(3'UTR)内的元件调节,这些元件对细胞周期依赖性信号作出反应。先前已经涉及到 mRNA 翻译的时间控制的一个元件是细胞质多聚腺苷酸化元件(CPE)。在这项研究中,我们表明 CPE 并不直接指导早期 mRNA 翻译。相反,早期翻译是通过特定的早期因子指导的,包括 Musashi 结合元件(MBE)和 Musashi 结合蛋白。我们的研究结果表明,尽管细胞周期蛋白 B5 3'UTR 包含 CPE 和 MBE,但 MBE 是早期翻译的关键调节剂。细胞周期蛋白 B2 3'UTR 含有 CPE,但缺乏 MBE,并且在成熟后期被翻译激活。最后,利用反义寡核苷酸来减弱内源性 Musashi 的合成,我们表明 Musashi 对于早期类 mRNA 翻译的起始以及随后的 CPE 依赖性 mRNA 翻译的激活至关重要。