Post-transcriptional regulation of transcript abundance by a conserved member of the tristetraprolin family in Candida albicans.
Post-transcriptional regulation of transcript abundance by a conserved member of the tristetraprolin family in Candida albicans.
复制标题
白色念珠菌中三四脯氨酸家族保守成员对转录本丰度的转录后调节。
DOI：
10.1111/mmi.12913
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发表时间：
2015
影响因子：
3.6
通讯作者：
Blackshear,PerryJ
中科院分区：
文献类型：
--
作者：
Wells,MelissaL;Washington,OnicaL;Hicks,StephanieN;Nobile,ClarissaJ;Hartooni,Nairi;Wilson,GeraldM;Zucconi,BethE;Huang,Weichun;Li,Leping;Fargo,DavidC;Blackshear,PerryJ
CCCH串联锌指蛋白的tristetraprolin（TTP）家族成员与靶mRNA中富含Au的区域结合，导致其去腺苷化和衰变。酿酒酵母中的家族成员影响铁代谢，而粟酒裂殖酵母中表达的单一蛋白质Zfs 1调节细胞-细胞相互作用。在人类病原体白色念珠菌中，对缺乏orthogonal蛋白Zfs 1的突变体进行深度测序，发现156个转录本显着增加（> 1.5倍）。其中，113个（72%）在其3′UTR中含有至少一个预测的TTP家族成员结合位点，而56个下调转录本中只有3个（5%）。Zfs 1 Δ/Δ突变体对3-氨基-1，2，4-三唑具有抗性，这可能是由于HIS 3编码的潜在靶转录物的表达增加。Zfs 1靶基因编码的蛋白序列在真菌CTG进化枝内的其他物种中高度保守，而这些mRNA中预测的Zfs 1结合位点往往随着与亲本物种进化距离的增加而“消失”。白色念珠菌Zfs 1与理想的哺乳动物TTP结合位点具有高亲和力，并且Zfs 1在免疫共沉淀后与靶转录物结合。因此，这些蛋白质在真菌中的生化活性是高度保守的，但Zfs 1样蛋白可能靶向每个物种的不同转录本。
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 inSaccharomyces cerevisiaeinfluence iron metabolism, whereas the single protein expressed inSchizosaccharomyces pombe, Zfs1, regulates cell–cell interactions. In the human pathogenCandida albicans, deep sequencing of mutants lacking the orthologous protein, Zfs1, 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. Thezfs1Δ/Δmutant was resistant to 3‐amino‐1,2,4‐triazole, perhaps because of increased expression of the potential target transcript encoded byHIS3. Sequences of the proteins encoded by the putative Zfs1 targets were highly conserved among other species within the fungal CTG clade, while the predicted Zfs1 binding sites in these mRNAs often ‘disappeared’ with increasing evolutionary distance from the parental species.C. albicansZfs1 bound to the ideal mammalian TTP binding site with high affinity, and Zfs1 was associated with target transcripts after co‐immunoprecipitation. Thus, the biochemical activities of these proteins in fungi are highly conserved, but Zfs1‐like proteins may target different transcripts in each species.