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J Biol Chem. 2007 Oct 12;282(41):30070-7. Epub 2007 Aug 21.

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

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  • 1Harvard Medical School, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Abstract

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.

PMID:
17711853
[PubMed - indexed for MEDLINE]
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