T-cell intracellular antigen-1 (TIA-1)-induced translational silencing promotes the decay of selected mRNAs

Gene array analysis revealed that a subset of mRNAs overexpressed in macrophages lacking the destabilizing factor TTP are also overexpressed in macrophages lacking the translational silencer TIA-1. We confirmed that a representative transcript, apobec-1, is significantly stabilized in cells lacking TIA-1. Tethering TIA-1 to a reporter transcript also promotes mRNA decay, suggesting that TIA-1- mediated translational silencing can render mRNA susceptible to the decay machinery. TIA-1- mediated decay is inhibited by small interfering RNAs targeting components of either the 5 '-3 ' ( e. g. DCP2) or the 3 '-5 ' ( e. g. exosome component Rrp46) decay pathways, suggesting that TIA-1 renders mRNA susceptible to both major decay pathways. TIA-1 mediated decay is inhibited by cycloheximide and emetine, drugs that stabilize polysomes, but is unaffected by puromycin, a drug that disassembles polysomes. These results suggest that TIA-1-induced polysome disassembly is required for enhanced mRNA decay and that TIA-1-induced translational silencing promotes the decay of selected mRNAs.