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Post‐transcriptional regulation of transcript abundance by a conserved member of the tristetraprolin family in C andida albicans
Author(s) -
Wells Melissa L.,
Washington Onica L.,
Hicks Stephanie N.,
Nobile Clarissa J.,
Hartooni Nairi,
Wilson Gerald M.,
Zucconi Beth E.,
Huang Weichun,
Li Leping,
Fargo David C.,
Blackshear Perry J.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12913
Subject(s) - tristetraprolin , biology , family member , abundance (ecology) , genetics , messenger rna , gene , ecology , rna binding protein , medicine , family medicine
Summary Members of the tristetraprolin ( TTP ) family of CCCH tandem zinc finger proteins bind to AU ‐rich regions in target mRNAs , leading to their deadenylation and decay. Family members in S accharomyces cerevisiae influence iron metabolism, whereas the single protein expressed in S chizosaccharomyces pombe , Z fs1, regulates cell–cell interactions. In the human pathogen C andida albicans , deep sequencing of mutants lacking the orthologous protein, Z fs1, revealed significant increases (> 1.5‐fold) in 156 transcripts. Of these, 113 (72%) contained at least one predicted TTP family member binding site in their 3′ UTR , compared with only 3 of 56 (5%) down‐regulated transcripts. The zfs1Δ/Δ mutant was resistant to 3‐amino‐1,2,4‐triazole, perhaps because of increased expression of the potential target transcript encoded by HIS 3 . Sequences of the proteins encoded by the putative Z fs1 targets were highly conserved among other species within the fungal CTG clade, while the predicted Z fs1 binding sites in these mRNAs often ‘disappeared’ with increasing evolutionary distance from the parental species. C . albicans Z fs1 bound to the ideal mammalian TTP binding site with high affinity, and Z fs1 was associated with target transcripts after co‐immunoprecipitation. Thus, the biochemical activities of these proteins in fungi are highly conserved, but Z fs1‐like proteins may target different transcripts in each species.