The role of AUF1 in regulated mRNA decay

Abstract

Messenger ribonucleic acid (mRNA) turnover is a major control point in gene expression. In mammals, many mRNAs encoding 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/degradation factor 1 (AUF1), one of the best-characterized AUBPs, binds to many ARE-mRNAs and assembles other factors necessary to recruit the mRNA degradation machinery. These factors include translation initiation factor eIF4G, chaperones hsp27 and hsp70, heat-shock cognate protein hsc70, lactate dehydrogenase, poly(A)-binding protein, and other unidentified proteins. Numerous signaling pathways alter the composition of this AUF1 complex of proteins to effect 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 AUF1 involvement in AMD.

Arginine methylation enhances the RNA chaperone activity of the West Nile virus host factor AUF1 p45

“…Four AUF1 isoforms are generated by alternative splicing from a common pre-mRNA (Wagner et al 1998); according to their apparent molecular masses, they were named p37, p40, p42, and p45, respectively. The isoforms show differences in their phosphorylation pattern as well as in nuclear-cytoplasmic shuttling and ARE-binding; these differences are suspected to affect their activities in transcriptional and post-transcriptional regulation of gene expression (Wilson et al 2001(Wilson et al , 2003Tolnay et al 2002;Raineri et al 2004;Gratacos and Brewer 2010;Zucconi et al 2010). All isoforms share two tandemly arranged RRMs and an arginine-glycine-rich region, RGG/ RG motif, within the C terminus (see Fig.…”

Investigating the potential immune role of fish NCAMs: Molecular cloning and expression analysis in mandarin fish

“…For that the mRNAs of many inflammatory mediators and cytokines expressed upon inflammation contain AREs, which promote degradation [39,40], we suspect that mfNCAM1a transcript should be more stable than mfNCAM2 and mfNCAM1b, among the head kidneyoriginated members. On the other hand, the existence of VASE sequence in head kidney-originated mfNCAM1b may indicate alteration in NCAM-mediated cellecell interaction [41], since VASE was reported to inhibit NCAM-dependent adhesion [42].…”

ING4 inhibits the translation of proto‐oncogene MYC by interacting with AUF1

“…AU-rich RNA-binding factor 1 (AUF1 also known as heterogeneous nuclear ribonucleoprotein D, hnRNP D) is an ARE-binding protein family that consists of four isoforms. AUF1 proteins affect mRNA turnover by assembling other factors in vivo [15]. All four AUF1 isoforms interact with heat-shock proteins hsc70/hsp70, translation initiation factor eIF4G and poly(A)-binding protein (PABP) [16][17][18].…”