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Gene expression differences in mouse placenta tissue between wild-type and Zfp36l3 knockout mice

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The ZFP36L3 protein is a rodent-specific, placenta- and yolk sac-specific member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins. These proteins bind to AU-rich elements in target mRNAs, and promote their deadenylation and decay. Mice deficient in ZFP36L3 exhibited decreased neonatal survival rates, but no apparent morphological changes in the placenta or surviving offspring. Zfp36l3 is paternally imprinted, with profound parent-of-origin effects on gene expression. RNASeq of KO placental mRNA revealed many significantly affected transcripts, some of which exhibited decreased decay rates in differentiated trophoblast stem cells derived from KO blastocysts. The type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite an increase in its stability. This receptor is critical for placental iron uptake from the maternal circulation, and its decrease was accompanied by decreased iron stores in the KO fetus, suggesting that this intrauterine deficiency might have deleterious consequences in later life. Examination of gene expression differences in mouse placenta tissue between wild-type and Zfp36l3 knockout groups, each with 5 biological replicates

ZFP36L3蛋白属于CCCH型串联锌指蛋白(CCCH tandem zinc finger proteins)家族的齐三脯氨酸蛋白(Tristetraprolin, TTP)亚家族,是一种啮齿动物特异性、胎盘及卵黄囊特异性的成员。这类蛋白可结合靶mRNA中的AU富集元件,并促进其脱腺苷酸化与降解。ZFP36L3敲除小鼠的新生存活率显著降低,但胎盘与存活子代未出现明显形态学异常。Zfp36l3属于父本印记基因,对基因表达具有显著的亲本起源依赖性调控效应。对敲除型(KO)胎盘mRNA开展RNA测序(RNASeq)分析,结果显示大量转录本的表达水平发生显著改变;其中部分转录本在源自敲除型囊胚的分化滋养层干细胞中,降解速率出现下降。尽管1型转铁蛋白受体mRNA的稳定性有所提升,但在敲除型胎盘中其表达水平却意外下调。该受体是胎盘从母体循环系统摄取铁离子的关键蛋白;敲除型胎盘中该受体的表达降低,伴随敲除型胎儿体内铁储备减少,提示这种宫内铁缺乏可能对其后续生命健康产生不良影响。本数据集针对野生型与Zfp36l3敲除型两组小鼠的胎盘组织开展基因表达差异分析,每组均包含5个生物学重复样本。

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