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Regulation of ARE transcript 3′ end processing by the yeast Cth2 mRNA decay factor
Author(s) -
Prouteau Manoël,
Daugeron MarieClaire,
Séraphin Bertrand
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.212
Subject(s) - biology , messenger rna , yeast , genetics , rna processing , saccharomyces cerevisiae , microbiology and biotechnology , computational biology , gene
Regulation of mRNA decay is an important step modulating gene expression. The stability of numerous eukaryotic mRNAs is controlled by adenosine/uridine‐rich elements (AREs) located in their 3′UTR. In Saccharomyces cerevisiae , the Cth2 protein stimulates the decay of target ARE mRNAs on iron starvation. Cth2, and its mammalian homologue tristetraprolin, contains a characteristic tandem CCCH zinc‐finger essential for ARE binding and mRNA decay. We have performed a structure–function analysis of Cth2 to understand the mechanism(s) by which it destabilizes mRNAs. This indicated that a conserved N‐terminal region of Cth2 is essential for its decay function but dispensable for RNA binding. Unexpectedly, Cth2 mutants lacking this domain blocked the normal 3′ end processing of ARE mRNAs leading to the formation of extended transcripts. These can also be detected in mutant of the polyadenylation machinery. Consistently, Cth2 localization in the nucleus suggests that it may interfere with poly(A) site selection. Our analysis reveal that ARE‐binding protein may affect mRNA 3′ end processing and that this contributes to mRNA destabilization.