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Stepwise assembly of the Nova-regulated alternative splicing network in the vertebrate brain

机译:脊椎动物大脑中Nova调控的选择性剪接网络的逐步组装

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摘要

Novel organismal structures in metazoans are often undergirded by complex gene regulatory networks; as such, understanding the emergence of new structures through evolution requires reconstructing the series of evolutionary steps leading to these underlying networks. Here, we reconstruct the step-by-step assembly of the vertebrate splicing network regulated by Nova, a splicing factor that modulates alternative splicing in the vertebrate central nervous system by binding to clusters of YCAY motifs on pre-RNA transcripts. Transfection of human HEK293T cells with Nova orthologs indicated vertebrate-like splicing regulatory activity in bilaterian invertebrates, thus Nova acquired the ability to bind YCAY clusters and perform vertebrate-like splicing modulation at least before the last common ancestor of bilaterians. In situ hybridization studies in several species showed that Nova expression became restricted to CNS later on, during chordate evolution. Finally, comparative genomics studies revealed a diverse history for A/ova-regulated exons, with target exons arising through both de novo exon creation and acquisition of YCAY motifs by preexisting exons throughout chordate and vertebrate history. In addition, we find that tissue-specific Nova expression patterns emerged independently in other lineages, suggesting independent assembly of tissue-specific regulatory networks.
机译:后生动物中的新型生物结构通常被复杂的基因调控网络所破坏。因此,要通过进化来了解新结构的出现,就需要重构导致这些基础网络的一系列进化步骤。在这里,我们重建了由Nova调控的脊椎动物剪接网络的分步装配,Nova是一个剪接因子,通过与前RNA转录物上的YCAY图案簇结合来调节脊椎动物中枢神经系统中的选择性剪接。用Nova直系同源物转染人HEK293T细胞表明,在双侧无脊椎动物中,脊椎动物具有类似的剪接调控活性,因此Nova至少在双侧人的最后一个共同祖先之前就具有结合YCAY簇并进行脊椎动物样剪接调节的能力。在几个物种中的原位杂交研究表明,Nova的表达后来在cho酸盐的进化过程中仅限于CNS。最后,比较基因组学研究揭示了由A / ova调控的外显子的不同历史,靶外显子是通过从头创建外显子和通过在整个cho酸盐和脊椎动物史中预先存在的外显子获得YCAY图案而产生的。此外,我们发现组织特异性Nova表达模式在其他谱系中独立出现,表明组织特异性调控网络的独立组装。

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    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain;

    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain;

    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain;

    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain;

    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain;

    Department for Molecular Evolution and Development,Center for Organismal Systems Biology, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria;

    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain;

    Department for Molecular Evolution and Development,Center for Organismal Systems Biology, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria;

    Department of Biology, Stanford University,Stanford, CA 94305;

    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain,Department for Molecular Evolution and Development,Center for Organismal Systems Biology, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria;

    Adepartament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona E08028, Spain,Department for Molecular Evolution and Development,Center for Organismal Systems Biology, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria;

  • 收录信息 美国《科学引文索引》(SCI);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
  • 关键词

    evo-devo; pasilla; amphioxus;

    机译:evo-devo;pasilla;两栖类;

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