AUF1 regulation of coding and noncoding RNA.
AUF1 regulation of coding and noncoding RNA.
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DOI：
10.1002/wrna.1393
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Wilson GM
中科院分区：
文献类型：
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作者：
White EJ;Matsangos AE;Wilson GM
AUF1是一个由4个rna结合蛋白组成的蛋白家族，由mRNA前剪接产生，在控制mRNA靶标的稳定性和/或翻译方面具有典型作用，基于对mRNA 3 '非翻译区富含au序列的识别。然而，最近在整个转录组中鉴定AUF1靶点的研究表明，这些规范功能只是其在基因表达转录后调控中作用的一个子集。在这篇综述中，我们描述了我们对AUF1的rna结合特性及其在指导mRNA衰变和翻译中的生化意义和作用的理解的最新进展。接下来是对新发现的控制miRNA合成和功能的AUF1蛋白活性的调查，包括miRNA组装成miRISC复合物，miRISC靶向mRNA底物，与其他细胞rna结合蛋白网络的相互作用，以及miRNA和AUF1合成之间的相互调节关系。最后，我们讨论了最近报道的AUF1与长链非编码RNA之间的关系以及对病毒RNA底物的调节作用。总的来说，这些发现极大地扩展了我们对细胞中AUF1功能的范围和多样性的认识，并推动了一系列令人兴奋的新问题向前发展。AUF1增强了选择的mirna装载到RISC复合物中，但也可以调节miRISC对mRNA底物的访问。
AUF1 is a family of four RNA-binding proteins generated by alternative pre-mRNA splicing, with canonical roles in controlling the stability and/or translation of mRNA targets based on recognition of AU-rich sequences within mRNA 3′ untranslated regions. However, recent studies identifying AUF1 target sites across the transcriptome have revealed that these canonical functions are but a subset of its roles in posttranscriptional regulation of gene expression. In this review, we describe recent developments in our understanding of the RNA-binding properties of AUF1 together with their biochemical implications and roles in directing mRNA decay and translation. This is then followed by a survey of newly discovered activities for AUF1 proteins in control of miRNA synthesis and function, including miRNA assembly into miRISC complexes, miRISC targeting to mRNA substrates, interplay with an expanding network of other cellular RNA-binding proteins, and reciprocal regulatory relationships between miRNA and AUF1 synthesis. Finally, we discuss recently reported relationships between AUF1 and long noncoding RNAs and regulatory roles on viral RNA substrates. Cumulatively, these findings have significantly expanded our appreciation of the scope and diversity of AUF1 functions in the cell, and are prompting an exciting array of new questions moving forward. AUF1 enhances loading of select miRNAs into RISC complexes but can also regulate miRISC access to mRNA substrates.