Mechanisms coordinating ELAV/Hu mRNA regulons.

Mechanisms coordinating ELAV/Hu mRNA regulons.
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DOI:
10.1016/j.gde.2012.12.006
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发表时间:
2013-02
影响因子:
4
通讯作者:
Keene, Jack D.
Keene, Jack D.
中科院分区:
生物学2区
文献类型:
--
作者:
Simone, Laura E.;Keene, Jack D.

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信使 RNA (mRNA) 的 5' 和 3' 非翻译区 (UTR) 作为平台,可以单独或总体决定每个 mRNA 的命运。编码功能相关蛋白的多个 mRNA 通常与 RNA 结合蛋白 (RBP) 和非编码 RNA (ncRNA) 相互作用,这些蛋白在时间和空间上协调它们的表达,作为核糖核蛋白 (RNP) 基础设施(我们称为核糖体)内的 RNA 调节子。最近出现的核糖组学方法可以确定哪些 mRNA 被 RBP 和 ncRNA 结合和调节,其中一些结合起来确定全局结果。 ELAV/Hu 蛋白与 mRNA 中富含 AU 的元件 (ARE) 结合,并调节其从剪接到翻译的稳定性,而普遍存在的 HuR 蛋白与癌细胞生长有关。最近的工作重点是 ELAV/Hu 蛋白如何通过基于 ARE 的核糖核小体抑制 microRNA (miR) 和 RNA 诱导沉默复合物 (RISC) 来增加 mRNA 稳定性和翻译,从而可能影响 mRNA 调节子的整体功能。
The 5’ and 3’ untranslated regions (UTRs) of messenger RNAs (mRNAs) function as platforms that can determine the fate of each mRNA individually and in aggregate. Multiple mRNAs that encode proteins that are functionally related often interact with RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) that coordinate their expression in time and space as RNA regulons within the ribonucleoprotein (RNP) infrastructure we term the ribonome. Recent ribonomic methods have emerged that can determine which mRNAs are bound and regulated by RBPs and ncRNAs, some of which act in combination to determine global outcomes. ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth. Recent work is focused on mechanistic models of how ELAV/Hu proteins increase mRNA stability and translation by repressing microRNAs (miRs) and the RNA induced silencing complex (RISC) via ARE-based ribonucleosomes that may affect global functions of mRNA regulons.
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