Post-transcriptional control of gene expression by AUF1: Mechanisms, physiological targets, and regulation

• Published in: Biochimica et biophysica acta Vol. 1829; no. 6-7; pp. 680 - 688
• Main Authors: White, Elizabeth J.F., Brewer, Gary, Wilson, Gerald M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2013
• Subjects: Alternative splicing; Alternative Splicing - genetics; AU Rich Elements - genetics; AU-rich element; Gene Expression Regulation; Gene regulation; Heterogeneous-Nuclear Ribonucleoprotein D - genetics; Humans; mRNA turnover; Protein Processing, Post-Translational; RNA Precursors - genetics; RNA Stability - genetics; RNA structure; RNA, Messenger - genetics; RNA-binding protein; Alternative splicing; RNA-binding protein; RNA structure; AU-rich element; mRNA turnover; Gene regulation
• ISSN: 1874-9399; 0006-3002; 1876-4320
• DOI: 10.1016/j.bbagrm.2012.12.002

AUF1 is a family of four proteins generated by alternative pre-mRNA splicing that form high affinity complexes with AU-rich, mRNA-destabilizing sequences located within the 3′ untranslated regions of many labile mRNAs. While AUF1 binding is most frequently associated with accelerated mRNA decay, emerging examples have demonstrated roles as a mRNA stabilizer or even translational regulator for specific transcripts. In this review, we summarize recent advances in our understanding of mRNA recognition by AUF1 and the biochemical and functional consequences of these interactions. In addition, unique properties of individual AUF1 isoforms and the roles of these proteins in modulating expression of genes associated with inflammatory, neoplastic, and cardiac diseases are discussed. Finally, we describe mechanisms that regulate AUF1 expression in cells, and current knowledge of regulatory switches that modulate the cellular levels and/or activities of AUF1 isoforms through distinct protein post-translational modifications. This article is part of a Special Issue entitled: RNA Decay mechanisms. ► AUF1 is an RNA-binding factor that regulates expression of targeted transcripts. ► AUF1 binding is influenced by and impacts local RNA structure. ► AUF1 nucleates assembly of multi-subunit trans-acting complexes on RNA substrates. ► Many AUF1 target mRNAs encode clinically important factors. ► AUF1 expression, isoform distribution, and activity are tightly regulated.