Translational Repression by RNA-Binding Protein TIAR

Abstract

The RNA-binding protein TIAR has been proposed to inhibit protein synthesis transiently by promoting the formation of translationally silent stress granules. Here, we report the selective binding of TIAR to several mRNAs encoding translation factors such as eukaryotic initiation factor 4A (eIF4A) and eIF4E (translation initiation factors), eEF1B (a translation elongation factor), and c-Myc (which transcriptionally controls the expression of numerous translation regulatory proteins). TIAR bound the 3-untranslated regions of these mRNAs and potently suppressed their translation, particularly in response to low levels of short-wavelength UV (UVC) irradiation. The UVC-imposed global inhibition of the cellular translation machinery was significantly relieved after silencing of TIAR expression. We propose that the TIAR-mediated inhibition of translation factor expression elicits a sustained repression of protein biosynthesis in cells responding to stress.

Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR

“…lanes 6,7 and lane 5, input samples are shown in lanes 1-4). In addition, mRNAs for calmodulin 2 and b-actin, which lack 59TOPs but have previously been described to bear TIA-1-and TIARbinding sites in their 39 UTRs (Lopez de Silanes et al 2005;Mazan-Mamczarz et al 2006;Kim et al 2007), served as positive controls, and both copurify with TIA-1 and TIAR as expected (Fig. 1A, middle panels).…”

“…Based on previous studies implicating TIA-1 and TIAR in translational repression (Piecyk et al 2000 Kim et al 2007) and in binding to pyrimidine-rich sequences (Dember et al 1996;Lopez de Silanes et al 2005;Mazan-Mamczarz et al 2006;Kim et al 2007Kim et al , 2011, we speculated that TIA-1 and TIAR may play a role in the control of 59TOP mRNA translation. To first determine whether TIA-1 and TIAR exist in complex with 59TOP mRNAs, we established human HEK293 cell lines stably expressing Flagtagged TIA-1 or TIAR under control of tetracycline-inducible promoters.…”

Nucleocytoplasmic Traffic of CPEB1 and Accumulation in Crm1 Nucleolar Bodies

“…For instance, Rck/p54 which is essential for the repression of maternal mRNA in the cytoplasm in combination with CPEB1 (Minshall et al, 2001), is both nuclear and cytoplasmic in early Xenopus oocytes (Smillie and Sommerville, 2002). Such a dual localization is observed for various factors, including CUG-BP/EDEN-BP (Fujimura et al, 2008), TIA1 (Lopez de Silanes et al, 2005;Zhang et al, 2005), TIAR (Mazan-Mamczarz et al, 2006), FMRP, FXR1, and FXR2 (Eberhart et al, 1996;Tamanini et al, 1999). In some cases, for This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -09 -0904) on October 15, 2008. instance CUG-BP/EDEN-BP, TIA1, and TIAR, it reflects a dual function of the protein in both translation and splicing (Philips et al, 1998;Le Guiner et al, 2001).…”

Genome-wide Analysis Identifies Interleukin-10 mRNA as Target of Tristetraprolin

“…As an unbiased approach, RNA can be isolated from affinity-purified RNA-binding proteins (RNA immunoprecipitation (RIP)) and subjected to genome-scale microarray analysis (RIP-Chip) (25,26). This strategy has revealed the spectrum of mRNAs associated with several RNA-binding proteins including HuB, eIF4E, PABP (27), FMRP (28), Puf (29), TIA-1 (30), and TIAR (31). In this report we have used RIP-Chip to identify transcripts that associate with TTP in macrophages activated by lipopolysaccharide (LPS).…”