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PMID: 17178830 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

An unconventional human Ccr4-Caf1 deadenylase complex in nuclear cajal bodies.

Molecular and cellular biology ·Vol. 27 ·No. 5 ·2007-03-00 ·Pages 1686-95

Wagner E, Clement SL, Lykke-Andersen J

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.

MeSH Terms
Animals Cell Line Cell Nucleus/enzymology,metabolism Coiled Bodies/enzymology,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,metabolism Substrate Specificity Transcription Factors/metabolism
Chemicals
CNOT8 protein, human Nuclear Proteins RNA, Messenger Recombinant Fusion Proteins Transcription Factors nocturnin Green Fluorescent Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wagner Eileen
MCD Biology, University of Colorado, Boulder, CO 80309, USA.
Clement Sandra L
Lykke-Andersen Jens
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.01483-06
Published
2007-03-00
Epub
2006-00-18
Pages
1686-95
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1820451
Subset
IM
Grants
NIGMS NIH HHS · R01 GM066811 · United States
NIGMS NIH HHS · T32 GM007135 · United States
NIGMS NIH HHS · GM 066811 · United States
NIGMS NIH HHS · GM-07135 · United States
External Links
PubMed source DOI: 10.1128/MCB.01483-06 PMC Full Text View journal details
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