RNA-Mediated Regulation of HMGA1 Function.
RNA-Mediated Regulation of HMGA1 Function.
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DOI：
10.3390/biom5020943
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发表时间：
2015
期刊：
影响因子：
5.5
通讯作者：
Eilebrecht S
中科院分区：
文献类型：
--
作者：
Benecke AG;Eilebrecht S
高迁移率族蛋白A1（HMGA 1）是染色质结构的主要调节因子，通过与位于多种基因的启动子和增强子区域中的富含A/T的DNA序列直接相互作用来介导其主要基因调节活性。HMGA 1 DNA通过三个AT钩基序结合导致开放的染色质结构，随后导致基因表达的变化。除了其在发育过程中的显著表达外，HMGA 1在几乎所有癌症中都过表达，其中HMGA 1表达水平与肿瘤恶性程度相关。HMGA 1的外源性过表达可导致恶性细胞转化，使该蛋白在癌症发生过程中发挥关键作用。最近的研究揭示了HMGA 1与细胞和病毒RNA的高度特异性竞争性相互作用，也通过蛋白质的AT-钩结构域，显着影响HMGA 1依赖的基因表达。在这篇综述中，我们讨论了HMGA 1-RNA复合物在转录和表观基因组调控过程中的结构和功能及其在HMGA 1相关疾病中的意义。
The high mobility group protein A1 (HMGA1) is a master regulator of chromatin structure mediating its major gene regulatory activity by direct interactions with A/T-rich DNA sequences located in the promoter and enhancer regions of a large variety of genes. HMGA1 DNA-binding through three AT-hook motifs results in an open chromatin structure and subsequently leads to changes in gene expression. Apart from its significant expression during development, HMGA1 is over-expressed in virtually every cancer, where HMGA1 expression levels correlate with tumor malignancy. The exogenous overexpression of HMGA1 can lead to malignant cell transformation, assigning the protein a key role during cancerogenesis. Recent studies have unveiled highly specific competitive interactions of HMGA1 with cellular and viral RNAs also through an AT-hook domain of the protein, significantly impacting the HMGA1-dependent gene expression. In this review, we discuss the structure and function of HMGA1-RNA complexes during transcription and epigenomic regulation and their implications in HMGA1-related diseases.