Regulation of the mRNAs encoding proteins of the BMP signaling pathway during the maternal stages of Xenopus development

Regulation of the mRNAs encoding proteins of the BMP signaling pathway during the maternal stages of Xenopus development
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DOI:
10.1006/dbio.2001.0324
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发表时间:
2001-08-01
影响因子:
2.7
通讯作者:
Sheets, MD
Sheets, MD
中科院分区:
生物学3区
文献类型:
--
作者:
Fritz, BR;Sheets, MD

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非洲爪蟾骨形态发生蛋白(BMP)通路的激活与合子转录的开始是一致的,但需要母体信号蛋白。通过使用多核糖体结合作为翻译活性的测定来研究控制编码BMP途径的蛋白质的mRNA的翻译的机制。我们的研究结果表明,五种不同的mRNA编码蛋白的BMP途径的非洲爪蟾发育过程中受到抑制性调节。这些mRNA与卵母细胞中的多聚核糖体不相关或无效相关,并且每个mRNA在不同的发育阶段被招募到多聚核糖体。Smad 1和ALK-2 mRNA在卵母细胞成熟过程中被募集到多核糖体中,而BMP-7和XSTK 9 mRNA在胚胎发生的早期阶段被募集。ALK-3 mRNA在任何母体发育阶段均未与多聚核糖体有效相关,仅在合子转录开始后有效募集至多聚核糖体。一般而言,对于除卵母细胞外的所有阶段,多聚核糖体募集与3' poly(A)尾的存在相关。然而,poly(A)的绝对长度与多聚体募集效率之间没有明显的相关性,表明poly(A)尾长与青蛙胚胎早期发育中的翻译之间的关系是复杂的。我们进一步关注BMP-7 mRNA,并证明了3 'UTR内的序列元件对于BMP-7 mRNA向多聚核糖体的募集是必需的,并且足以指导poly(A)的添加并在胚胎发生期间激活报告基因的翻译。有趣的是,BMP-7 mRNA缺乏先前定义的eCPE序列,该序列被提议在胚胎发生期间指导poly(A)添加和翻译激活。我们的研究结果在胚胎发育过程中的母体mRNA的翻译调控和BMP通路的激活的影响进行了讨论。(C)北京:科学出版社.
Activation of the Xenopus bone morphogenetic protein (BMP) pathway is coincident with the onset of zygotic transcription but requires maternal signaling proteins. The mechanisms controlling the translation of mRNAs that encode proteins of the BMP pathway were investigated by using polysome association as an assay for translational activity. Our results indicate that five different mRNAs encoding proteins of the BMP pathway were translationally regulated during Xenopus development. These mRNAs were either not associated or inefficiently associated with polysomes in oocytes, and each was recruited to polysomes at a different developmental stage. The Smad1 and ALK-2 mRNAs were recruited to polysomes during oocyte maturation, whereas the BMP-7 and XSTK9 mRNAs were recruited during the early stages of embryogenesis. The ALK-3 mRNA was not efficiently associated with polysomes during any maternal stage of development and was efficiently recruited to polysomes only after the onset of zygotic transcription. In general, for all stages except oocytes, polysome recruitment was associated with the presence of a 3' poly(A) tail. However, there was not an obvious correlation between the absolute length of poly(A) and the efficiency of polysome recruitment, indicating that the relationship between poly(A) tail length and translation during early frog embryogenesis is complex. We further focused on the BMP-7 mRNA and demonstrated that sequence elements within the 3'UTR were necessary for recruitment of the BMP-7 mRNA to polysomes and sufficient to direct the addition of poly(A) and activate translation of a reporter during embryogenesis. Interestingly, the BMP-7 mRNA lacks the previously defined eCPE sequences proposed to direct poly(A) addition and translational activation during embryogenesis. The implications of our findings for translational regulation of maternal mRNAs during embryogenesis and for the activation of the BMP pathway are discussed. (C) 2001 Academic Press.