Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability
Copyright policy )Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability
AU-rich elements (AREs) in the 3' untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in microRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-alpha. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. We further observed that miR16, a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, is required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay is sequence-specific and requires the ARE binding protein tristetraprolin (TTP). TTP does not directly bind to miR16 but interacts through association with Ago/eiF2C family members to complex with miR16 and assists in the targeting of ARE. miRNA targeting of ARE, therefore, appears to be an essential step in ARE-mediated mRNA degradation.
- Scripps Research Institute United States
- Xiamen University China (People's Republic of)
- Hong Kong Polytechnic University China (People's Republic of)
- Changhai Hospital China (People's Republic of)
- Novartis (Switzerland) Switzerland
Ribonuclease III, 571, Macromolecular Substances, RNA Stability, SEQUENCE, EXOSOME, Cell Line, Immediate-Early Proteins, CLONING, MAMMALIAN-CELLS, HUR, Animals, Drosophila Proteins, Humans, RNA-Induced Silencing Complex, RNA, Messenger, Eukaryotic Initiation Factors, 3' Untranslated Regions, TRISTETRAPROLIN, INTERFERENCE, Cell Nucleus, Base Sequence, Biochemistry, Genetics and Molecular Biology(all), DEGRADATION, DNA-Binding Proteins, BINDING-PROTEIN, MicroRNAs, Drosophila melanogaster, Gene Expression Regulation, Argonaute Proteins, C-ELEGANS, HeLa Cells
Ribonuclease III, 571, Macromolecular Substances, RNA Stability, SEQUENCE, EXOSOME, Cell Line, Immediate-Early Proteins, CLONING, MAMMALIAN-CELLS, HUR, Animals, Drosophila Proteins, Humans, RNA-Induced Silencing Complex, RNA, Messenger, Eukaryotic Initiation Factors, 3' Untranslated Regions, TRISTETRAPROLIN, INTERFERENCE, Cell Nucleus, Base Sequence, Biochemistry, Genetics and Molecular Biology(all), DEGRADATION, DNA-Binding Proteins, BINDING-PROTEIN, MicroRNAs, Drosophila melanogaster, Gene Expression Regulation, Argonaute Proteins, C-ELEGANS, HeLa Cells
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