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首页> 外文期刊>Nature >MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation
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MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation

机译：用于Nanog，Oct4和Sox2编码区的MicroRNA调节胚胎干细胞分化

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摘要

MicroRNAs (miRNAs) are short RNAs that direct messenger RNA degradation or disrupt mRNA translation in a sequence-dependent manner. For more than a decade, attempts to study the interaction of miRNAs with their targets were confined to the 3' untranslated regions of mRNAs, fuelling an underlying assumption that these regions are the principal recipients of miRNA activity. Here we focus on the mouse Nanog, Oct4 (also known as Pou5fl) and Sox2 genes and demonstrate the existence of many naturally occurring miRNA targets in their amino acid coding sequence (CDS). Some of the mouse targets analysed do not contain the miRNA seed, whereas others span exon-exon junctions or are not conserved in the human and rhesus genomes. miR-134, miR-296 and miR-470, upregulated on retinoic-acid-induced differentiation of mouse embryonic stem cells, target the CDS of each transcription factor in various combinations, leading to transcriptional and morphological changes characteristic of differentiating mouse embryonic stem cells, and resulting in a new phenotype. Silent mutations at the predicted targets abolish miRNA activity, prevent the downregulation of the corresponding genes and delay the induced phenotype. Our findings demonstrate the abundance of CDS-located miRNA targets, some of which can be species-specific, and support an augmented model whereby animal miRNAs exercise their control on mRNAs through targets that can reside beyond the 3' untranslated region.
机译：微小RNA（miRNA）是短信使RNA，以序列依赖性方式指导信使RNA降解或破坏mRNA翻译。十多年来，研究miRNA与靶标相互作用的尝试仅限于mRNA的3'非翻译区，这加剧了一个基本的假设，即这些区域是miRNA活性的主要受体。在这里，我们重点研究小鼠Nanog，Oct4（也称为Pou5fl）和Sox2基因，并证明其氨基酸编码序列（CDS）中存在许多天然存在的miRNA靶标。分析的某些小鼠靶标不含miRNA种子，而其他一些跨越外显子-外显子连接或在人类和恒河猴基因组中不保守。在视黄酸诱导的小鼠胚胎干细胞分化中上调的miR-134，miR-296和miR-470，以各种组合靶向每种转录因子的CDS，从而导致分化的小鼠胚胎干细胞的转录和形态变化特征，并产生新的表型。预测靶标上的沉默突变消除了miRNA活性，防止了相应基因的下调并延迟了诱导的表型。我们的发现表明，位于CDS上的miRNA靶标丰富，其中一些可能是物种特异性的，并支持增强模型，其中动物miRNA通过可位于3'非翻译区之外的靶标对mRNA进行控制。

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  • 来源
    《Nature》 |2008年第7216期|p.1124-1128|共5页
  • 作者

    Yvonne Tay; Jinqiu Zhang; Andrew M. Thomson; Bing Lim; Isidore Rigoutsos;

  • 作者单位

    Stem Cell and Developmental Biology, Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), #08-01, Genome, 60 Biopolis Street, Singapore 138672, Singapore;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 关键词

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