RNA 结合因子 AUF1调控基因表达及其在肿瘤发生中的双重调控作用的研究进展

The role of RNA-binding factor AUF1 in regulated gene expression and modulation of tumorigenesis

信使RNA（ Messenger ribonucleic acid ，mRNA）不断更新在基因表达中具有重要作用，而且编码一些重要蛋白。本文详细阐述了RNA结合因子1（RNA-binding factor 1，AUF1）使mRNA稳定或去稳定，在转录后水平调控基因表达的可能的分子机制，归纳了AUF1各个亚型蛋白在基因表达中的独特作用的相关研究进展，并探讨了AUF1表达水平的改变在肿瘤发生中的双重调控作用。认识到AUF1发挥生物学效应的分子机制以及作用的具体信号通路，能够帮助我们揭开更多的生命谜题。

Turn-over of messenger ribonucleic acid （ mRNA） is a major control point in gene expres-sion.In mammals,many mRNAs encode inflammatory cytokines ,oncoproteins,and G-protein-coupled receptors are destabilized by the presence of AU -rich elements （ AREs ） in their 3′-untranslated regions .Association of ARE-binding proteins（AUBPs）with these mRNAs promotes rapid mRNA degradation .ARE/poly（U）-binding factor 1（AUF1）,one of the best-characterized AUBPs,binds to many ARE-mRNAs and assembles other fac-tors to recruit the mRNA degradation machinery .Most studies support an mRNA -destabilizing role for AUF1,al-though other findings suggest additional functions for this factor .However,several lines of evidence also support a role for AUF1 in the initiation and/or development of cancer .Many AUF1-targeted transcripts encode products that control pro-or anti-oncogenic processes .Numerous signaling pathways alter the composition of this AUF 1 complex of proteins to affect changes in ARE -mRNA degradation rates .This review briefly describes the roles of mRNA decay in gene expression in general and ARE -mediated decay （ AMD） in particular ,with a focus on AUF1 and the different modes of regulation that govern AUF 1 involvement in AMD.In the end,we discuss how changes in AUF1 isoform distribution,subcellular localization,and post-translational protein modifications can influence the metabolism of targeted mRNAs .