The DNA-Binding High-Mobility Group Box Domain of Sox Family Proteins Directly Interacts with RNA In Vitro.

The DNA-Binding High-Mobility Group Box Domain of Sox Family Proteins Directly Interacts with RNA In Vitro.
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DOI:
10.1021/acs.biochem.2c00218
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发表时间:
2022-05-05
期刊:
影响因子:
2.9
通讯作者:
Batey, Robert T.
Batey, Robert T.
中科院分区:
生物学3区
文献类型:
--
作者:
Hamilton, Desmond J.;Hein, Abigail E.;Holmes, Zachariah E.;Wuttke, Deborah S.;Batey, Robert T.

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越来越多的证据表明,大量被归类为DNA结合的蛋白质结构域也与RNA相互作用以调节生物过程。最近的几项研究表明,Sox2转录因子在体外和体内通过其高迁移率族盒(HMGB)结构域与RNA结合。在Sox转录因子家族成员中,该结构域的高度保守性表明RNA结合活性可能是这些蛋白质的一个普遍特征。为了验证这一假设,我们检测了人类Sox家族蛋白质中的一部分HMGB结构域在体外结合DNA和RNA的能力。我们观察到Sox家族HMGB结构域与各种模型RNA元件之间存在选择性的高亲和力相互作用,这些RNA元件包括一个四向连接RNA、一个带有内部凸起的发夹RNA、G - 四链体RNA以及长链非编码RNA ES2的一个片段,已知ES2可直接与Sox2相互作用。重要的是,HMGB结构域与这些RNA配体的结合明显比非一致性双链DNA更紧密,在某些情况下,其亲和力可与它们的一致性双链DNA序列相媲美。这些数据表明,RNA结合是Sox转录因子家族的一个保守特征,有可能调节尚未被充分认识的生物学功能。
There is growing evidence that a substantial number of protein domains ascribed as DNA-binding also interact with RNA to regulate biological processes. Several recent studies have revealed that the Sox2 transcription factor binds RNA through its high mobility group box (HMGB) domain in vitro and in vivo. High conservation of this domain amongst members of the Sox family of transcription factors suggests that RNA-binding activity may be a general feature of these proteins. To address this hypothesis, we examined a subset of HMGB domains from human Sox family proteins for their ability to bind both DNA and RNA in vitro. We observed selective, high affinity interactions between Sox family HMGB domains and various model RNA elements including a four-way junction RNA, a hairpin RNA with an internal bulge, G-quadruplex RNA, and a fragment of the long non-coding RNA ES2, which is known to directly interact with Sox2. Importantly, the HMGB domains bind these RNA ligands significantly tighter than non-consensus dsDNA and in some cases with affinities rivaling their consensus dsDNA sequences. These data suggest that RNA-binding is a conserved feature of the Sox family of transcription factors with the potential to modulate unappreciated biological functions.
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