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PMID: 18442996 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A role for Caf1 in mRNA deadenylation and decay in trypanosomes and human cells.

Nucleic acids research ·Vol. 36 ·No. 10 ·2008-06-00 ·Pages 3374-88

Schwede A, Ellis L, Luther J, Carrington M, Stoecklin G, Clayton C

Abstract

The eukaryotic Ccr4/Caf1/Not complex is involved in deadenylation of mRNAs. The Caf1 and Ccr4 subunits both potentially have deadenylating enzyme activity. We investigate here the roles of Ccr4 and Caf1 in deadenylation in two organisms that separated early in eukaryotic evolution: humans and trypanosomes. In Trypanosoma brucei, we found a complex containing CAF1, NOT1, NOT2 and NOT5, DHH1 and a possible homologue of Caf130; no homologue of Ccr4 was found. Trypanosome CAF1 has deadenylation activity, and is essential for cell survival. Depletion of trypanosome CAF1 delayed deadenylation and degradation of constitutively expressed mRNAs. Human cells have two isozymes of Caf1: simultaneous depletion of both inhibited degradation of an unstable reporter mRNA. In both species, depletion of Caf1 homologues inhibited deadenylation of bulk RNA and resulted in an increase in average poly(A) tail length.

MeSH Terms
Animals Cell Line Exoribonucleases/antagonists & inhibitors,physiology Humans Poly A/metabolism Protein Subunits/chemistry,metabolism Protozoan Proteins/antagonists & inhibitors,genetics,physiology RNA Helicases/physiology RNA Interference RNA, Messenger/metabolism RNA, Protozoan/metabolism Ribonucleases/genetics,physiology Sequence Homology, Amino Acid Transcription Factors/antagonists & inhibitors,genetics,physiology Trypanosoma brucei brucei/enzymology,genetics,growth & development
Chemicals
CNOT8 protein, human Protein Subunits Protozoan Proteins RNA, Messenger RNA, Protozoan Transcription Factors Poly A Exoribonucleases Ribonucleases mRNA deadenylase RNA Helicases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schwede Angela
Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Ellis Louise
Luther Julia
Carrington Mark
Stoecklin Georg
Clayton Christine
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkn108
Published
2008-06-00
Epub
2008-00-27
Pages
3374-88
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2425496
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkn108 PMC Full Text View journal details
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