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PMID:11719186

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Citation

Chen, CY, Gherzi, R, Ong, SE, Chan, EL, Raijmakers, R, Pruijn, GJ, Stoecklin, G, Moroni, C, Mann, M and Karin, M (2001) AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107:451-64

Abstract

Inherently unstable mammalian mRNAs contain AU-rich elements (AREs) within their 3' untranslated regions. Although found 15 years ago, the mechanism by which AREs dictate rapid mRNA decay is not clear. In yeast, 3'-to-5' mRNA degradation is mediated by the exosome, a multisubunit particle. We have purified and characterized the human exosome by mass spectrometry and found its composition to be similar to its yeast counterpart. Using a cell-free RNA decay system, we demonstrate that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening. The mammalian exosome does not recognize ARE-containing RNAs on its own. ARE recognition requires certain ARE binding proteins that can interact with the exosome and recruit it to unstable RNAs, thereby promoting their rapid degradation.

Links

PubMed

Keywords

3' Untranslated Regions/genetics; Amino Acid Sequence; Animals; Base Pairing; Base Sequence; Cell-Free System; Gene Silencing/physiology; Genes, fos; Humans; Interleukin-2/genetics; Jurkat Cells/drug effects; Jurkat Cells/metabolism; Mammals/genetics; Molecular Sequence Data; Poly A/metabolism; RNA, Messenger/metabolism; RNA, Neoplasm/metabolism; RNA-Binding Proteins/physiology; Recombinant Fusion Proteins/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Thymine Nucleotides/pharmacology; Trans-Activators

Significance

Annotations

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

HUMAN:MTREX

colocalizes_with

GO:0000178: exosome (RNase complex)

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:EXOS2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15024

F

Seeded From UniProt

complete

HUMAN:EXOS2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q99547

F

Seeded From UniProt

complete

HUMAN:EXOS2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NPD3

F

Seeded From UniProt

complete

HUMAN:EXOS2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NQT5

F

Seeded From UniProt

complete

HUMAN:EXOS7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13868

F

Seeded From UniProt

complete

HUMAN:EXOS7

involved_in

GO:0006401: RNA catabolic process

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MPH6

colocalizes_with

GO:0000176: nuclear exosome (RNase complex)

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MPH6

colocalizes_with

GO:0000178: exosome (RNase complex)

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MPH6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13868

F

Seeded From UniProt

complete

HUMAN:EXOS4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13868

F

Seeded From UniProt

complete

HUMAN:EXOS3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13868

F

Seeded From UniProt

complete

HUMAN:TTP

involved_in

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

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TTP

involved_in

GO:0043488: regulation of mRNA stability

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TTP

NOT|colocalizes_with

GO:0000178: exosome (RNase complex)

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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