New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action.
New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action.
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对长非编码RNA SRA的新见解：生理功能和作用机制
DOI：
10.3389/fmed.2018.00244
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发表时间：
2018
影响因子：
3.9
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Sheng L;Ye L;Zhang D;Cawthorn WP;Xu B
长链非编码RNA（lncRNA）作为新的遗传/表观遗传调节因子正在出现，可以影响几乎所有的生理功能。在这里，我们专注于长的非编码类固醇受体RNA激活剂（SRA），包括新的见解，其对基因表达，细胞周期和分化的影响;这些如何与生理和疾病;以及这些影响的机制。我们讨论了SRA如何在核受体信号传导中作为RNA辅激活剂;它对类固醇生成、脂肪生成和肌细胞分化的影响;对乳腺癌和前列腺癌肿瘤发生的影响;最后，它通过几种信号传导途径调节肝脂肪变性的能力。全基因组分析表明，SRA调节脂肪细胞和乳腺癌细胞中的数百个靶基因，并与人类多能干细胞中的数千个基因组位点结合。最近的研究表明，SRA作为一个分子支架，并形成网络与众多的辅调节剂和染色质修饰调节剂在激活和抑制复合物。我们讨论了SRA独特的茎环二级结构的修饰对SRA功能的重要性，并强调了具有临床意义的各种SRA亚型和突变。最后，我们讨论了未来的方向，更好地了解SRA行动的分子机制，以及如何这可能导致新的诊断和治疗方法。
Long non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators that can impact almost all physiological functions. Here, we focus on the long non-coding steroid receptor RNA activator (SRA), including new insights into its effects on gene expression, the cell cycle, and differentiation; how these relate to physiology and disease; and the mechanisms underlying these effects. We discuss how SRA acts as an RNA coactivator in nuclear receptor signaling; its effects on steroidogenesis, adipogenesis, and myocyte differentiation; the impact on breast and prostate cancer tumorigenesis; and, finally, its ability to modulate hepatic steatosis through several signaling pathways. Genome-wide analysis reveals that SRA regulates hundreds of target genes in adipocytes and breast cancer cells and binds to thousands of genomic sites in human pluripotent stem cells. Recent studies indicate that SRA acts as a molecular scaffold and forms networks with numerous coregulators and chromatin-modifying regulators in both activating and repressive complexes. We discuss how modifications to SRA's unique stem-loop secondary structure are important for SRA function, and highlight the various SRA isoforms and mutations that have clinical implications. Finally, we discuss the future directions for better understanding the molecular mechanisms of SRA action and how this might lead to new diagnostic and therapeutic approaches.
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