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PMID:17178830

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Citation

Wagner, E, Clement, SL and Lykke-Andersen, J (2007) An unconventional human Ccr4-Caf1 deadenylase complex in nuclear cajal bodies. Mol. Cell. Biol. 27:1686-95

Abstract

mRNA deadenylation is a key process in the regulation of translation and mRNA turnover. In Saccharomyces cerevisiae, deadenylation is primarily carried out by the Ccr4p and Caf1p/Pop2p subunits of the Ccr4-Not complex, which is conserved in eukaryotes including humans. Here we have identified an unconventional human Ccr4-Caf1 complex containing hCcr4d and hCaf1z, distant human homologs of yeast Ccr4p and Caf1p/Pop2p, respectively. The hCcr4d-hCaf1z complex differs from conventional Ccr4-Not deadenylase complexes, because (i) hCaf1z and hCcr4d concentrate in nuclear Cajal bodies and shuttle between the nucleus and cytoplasm and (ii) the hCaf1z subunit, in addition to rapid deadenylation, subjects substrate RNAs to slow exonucleolytic degradation from the 3' end in vitro. Exogenously expressed hCaf1z shows both of those activities on reporter mRNAs in human HeLa cells and stimulates general mRNA decay when restricted to the cytoplasm by deletion of its nuclear localization signal. These observations suggest that the hCcr4d-hCaf1z complex may function either in the nucleus or in the cytoplasm after its nuclear export, to degrade polyadenylated RNAs, such as mRNAs, pre-mRNAs, or those RNAs that are polyadenylated prior to their degradation in the nucleus.

Links

PubMed PMC1820451 Online version:10.1128/MCB.01483-06

Keywords

Animals; Cell Line; Cell Nucleus/enzymology; Cell Nucleus/metabolism; Coiled Bodies/enzymology; Coiled Bodies/metabolism; Cytoplasm/metabolism; Green Fluorescent Proteins/metabolism; HeLa Cells; Humans; Mice; Models, Biological; NIH 3T3 Cells; Nuclear Proteins/metabolism; Plasmids; RNA, Messenger/metabolism; Recombinant Fusion Proteins/isolation & purification; Recombinant Fusion Proteins/metabolism; Substrate Specificity; Transcription Factors/metabolism

Significance

Annotations

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

HUMAN:ANGE2

located_in

GO:0015030: Cajal body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ANGE2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TOE1

located_in

GO:0015030: Cajal body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TOE1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TOE1

enables

GO:0004535: poly(A)-specific ribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TOE1

involved_in

GO:0090503: RNA phosphodiester bond hydrolysis, exonucleolytic

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TOE1

enables

GO:0000175: 3'-5'-exoribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TOE1

part_of

GO:0015030: Cajal body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TOE1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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