The Sox2 transcription factor binds RNA
The Sox2 transcription factor binds RNA
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DOI：
10.1038/s41467-020-15571-8
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发表时间：
2020-04-14
影响因子：
16.6
通讯作者：
Batey, Robert T.
中科院分区：
文献类型：
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作者：
Holmes, Zachariah E.;Hamilton, Desmond J.;Batey, Robert T.
某些转录因子被认为与RNA形成功能性相互作用，以促进基因表达的适当调控。Sox2是一种对维持多能性和神经发生至关重要的转录因子，已发现它与几种长链非编码RNA（lncRNAs）相关联，尽管这些相互作用是直接的还是通过其他蛋白质尚不清楚。在此我们证明，人Sox2在体外通过其高迁移率族（HMG）DNA结合结构域以高亲和力直接与其中一种lncRNA相互作用。这些相互作用主要是以非序列特异性的方式与双链RNA发生，由一个相似但不完全相同的相互作用表面介导。我们进一步通过对Sox2进行紫外线交联免疫沉淀确定Sox2在小鼠胚胎干细胞中直接结合RNA，并且利用RNA结合蛋白免疫沉淀测序（fRIP - seq）在体内鉴定出了一千多种Sox2 - RNA相互作用。总之，这些数据表明Sox2在体外和体内采用了一种高亲和力/低特异性的RNA结合模式。一些转录因子已被认为在功能上与RNA相互作用以促进基因表达的适当调控。在此作者证明人Sox2通过其HMG DNA结合结构域直接且高亲和力地与RNAs相互作用。
Certain transcription factors are proposed to form functional interactions with RNA to facilitate proper regulation of gene expression. Sox2, a transcription factor critical for maintenance of pluripotency and neurogenesis, has been found associated with several lncRNAs, although it is unknown whether these interactions are direct or via other proteins. Here we demonstrate that human Sox2 interacts directly with one of these lncRNAs with high affinity through its HMG DNA-binding domain in vitro. These interactions are primarily with double-stranded RNA in a non-sequence specific fashion, mediated by a similar but not identical interaction surface. We further determined that Sox2 directly binds RNA in mouse embryonic stem cells by UV-cross-linked immunoprecipitation of Sox2 and more than a thousand Sox2-RNA interactions in vivo were identified using fRIP-seq. Together, these data reveal that Sox2 employs a high-affinity/low-specificity paradigm for RNA binding in vitro and in vivo. Some transcription factors have been proposed to functionally interact with RNA to facilitate proper regulation of gene expression. Here the authors demonstrate that human Sox2 interact directly and with high affinity to RNAs through its HMG DNA-binding domain.