协调 ELAV/Hu mRNA 调控物的机制。
Mechanisms coordinating ELAV/Hu mRNA regulons.
机构信息
Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, United States.
出版信息
Curr Opin Genet Dev. 2013 Feb;23(1):35-43. doi: 10.1016/j.gde.2012.12.006. Epub 2013 Jan 9.
Abstract
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.
摘要
信使 RNA（mRNA）的 5' 和 3' 非翻译区（UTRs）作为平台，可以单独和总体上决定每个 mRNA 的命运。编码功能相关蛋白质的多个 mRNA 经常与 RNA 结合蛋白（RBPs）和非编码 RNA（ncRNAs）相互作用，作为核糖核蛋白（RNP）基础设施内的 RNA 调控子，在时间和空间上协调它们的表达，我们称之为核糖组。最近出现了核糖组学方法，可以确定哪些 mRNA 被 RBPs 和 ncRNAs 结合和调节，其中一些组合作用以确定全局结果。ELAV/Hu 蛋白与 mRNA 中的富含 AU 元件（ARE）结合，并调节它们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。最近的工作集中在 ELAV/Hu 蛋白通过基于 ARE 的核小体抑制 microRNAs（miRs）和 RNA 诱导沉默复合物（RISC）来增加 mRNA 稳定性和翻译的机制模型上，这可能会影响 mRNA 调控子的全局功能。
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