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PMID:15766526

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Citation

Jing, Q, Huang, S, Guth, S, Zarubin, T, Motoyama, A, Chen, J, Di Padova, F, Lin, SC, Gram, H and Han, J (2005) Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 120:623-34

Abstract

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.

Links

PubMed Online version:10.1016/j.cell.2004.12.038

Keywords

3' Untranslated Regions/genetics; Animals; Argonaute Proteins; Base Sequence/genetics; Cell Line; Cell Nucleus/genetics; Cell Nucleus/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster; Eukaryotic Initiation Factors; Gene Expression Regulation/genetics; HeLa Cells; Humans; Immediate-Early Proteins/genetics; Immediate-Early Proteins/metabolism; Macromolecular Substances/metabolism; MicroRNAs/genetics; RNA Stability/genetics; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA-Induced Silencing Complex/genetics; RNA-Induced Silencing Complex/metabolism; Ribonuclease III/genetics; Ribonuclease III/metabolism; Tristetraprolin

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TTP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UKV8

F

Seeded From UniProt

complete

HUMAN:TTP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9HCK5

F

Seeded From UniProt

complete

HUMAN:AGO4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P26651

F

Seeded From UniProt

complete

HUMAN:AGO2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P26651

F

Seeded From UniProt

complete

HUMAN:TTP

involved_in

GO:0061158: 3'-UTR-mediated mRNA destabilization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TTP

colocalizes_with

GO:0070578: RISC-loading complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TTP

enables

GO:0035925: mRNA 3'-UTR AU-rich region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TTP

involved_in

GO:2000637: positive regulation of gene silencing by miRNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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