Functional interplay between RNA-binding protein HuR and microRNAs.
Functional interplay between RNA-binding protein HuR and microRNAs.
复制标题
RNA结合蛋白HUR和microRNA之间的功能相互作用。
DOI：
10.2174/138920312801619394
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发表时间：
2012-06
影响因子：
2.8
通讯作者：
Gorospe M
中科院分区：
文献类型：
--
作者：
Srikantan S;Tominaga K;Gorospe M
哺乳动物RNA结合蛋白（RBP）HuR与许多编码蛋白质的mRNA相关，这些蛋白质在细胞分裂、细胞存活、免疫应答和分化中起作用。已知HuR稳定许多这些mRNA和/或调节它们的翻译，但HuR影响靶mRNA命运的分子过程在很大程度上是未知的。过去五年积累的证据表明，HuR对许多结合转录本的影响取决于HuR与相同mRNA相关的microRNA的相互作用。在这里，我们回顾了HuR和microRNAs的相互作用-竞争和合作-管理共享的目标mRNA的表达。如果HuR-mRNA相互作用占优势，HuR和microRNA之间的竞争通常会导致基因表达增强，如果microRNA保持相关，则会导致抑制。HuR和microRNA之间的合作导致共享mRNA的表达降低。我们还描述了通过microRNA调节HuR水平以及通过HuR调节microRNA水平。最后，我们讨论了HuR结合的mRNA与相邻的microRNA位点的转录组范围内的分析，并审查了新兴的机制，使microRNA赋予的多功能性和强度的转录后结果的HuR目标。
The mammalian RNA-binding protein (RBP) HuR associates with numerous mRNAs encoding proteins with roles in cell division, cell survival, immune response, and differentiation. HuR was known to stabilize many of these mRNAs and/or modulated their translation, but the molecular processes by which HuR affected the fate of target mRNAs was largely unknown. Evidence accumulated over the past five years has revealed that the influence of HuR on many bound transcripts depends on HuR's interplay with microRNAs which associate with the same mRNAs. Here, we review the interactions of HuR and microRNAs – both competitive and cooperative – that govern expression of shared target mRNAs. Competition between HuR and microRNAs typically results in enhanced gene expression if the HuR-mRNA interaction prevails, and in repression if the microRNA remains associated. Cooperation between HuR and microRNAs leads to lower expression of the shared mRNA. We also describe the regulation of HuR levels by microRNAs as well as the regulation of microRNA levels by HuR. Finally, we discuss transcriptome-wide analyses of HuR-bound mRNAs with neighboring microRNA sites, and review the emerging mechanisms whereby microRNAs confer versatility and strength to the post-transcriptional outcomes of HuR targets.