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.
Yamasaki
Satoshi
S
Harvard Medical School, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Stoecklin
Georg
G
Kedersha
Nancy
N
Simarro
Maria
M
Anderson
Paul
P
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D039102:Poly(A)-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1
D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human