Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation.
Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation.
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DOI：
10.1016/j.bbagrm.2016.04.001
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Fleming TP
中科院分区：
文献类型：
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作者：
Denisenko O;Lucas ES;Sun C;Watkins AJ;Mar D;Bomsztyk K;Fleming TP
细胞和生物体通过降低转录、翻译和DNA复制的总体速率来对营养缺乏做出反应。这种变化在多大程度上可以逆转，在很大程度上是未知的。我们研究了母体饮食限制对后代RNA合成的影响。在整个妊娠期或仅在着床前阶段饲喂低蛋白饮食，可降低激发期间胎儿体细胞组织中的细胞RNA含量，并在激发释放后使其在胎儿和成体组织中的含量超过对照。核糖体RNA（细胞RNA的主要成分）转录的变化是导致这种表型的原因，这一点可通过核糖体DNA位点的RNA聚合酶I密度和DNA甲基化的匹配改变来证明。核糖体转录因子Rrn3的细胞水平反映了rRNA的表达模式。在细胞培养实验中，Rrn3过表达减少rDNA甲基化和增加rRNA表达;抑制Rrn3活性后发生相反的情况。这些观察结果定义了一种新的机制，即植入前营养不良不可逆地改变了此后rDNA甲基化和Rrn3因子介导的过程中rRNA转录的基础速率。母体营养不良下调胎儿组织中rDNA的转录。与对照组相比，切换到正常饮食永久上调rDNA转录。这些变化由DNA甲基化和Pol I转录因子Rrn3介导。这一机制在植入前被激活。
Cells and organisms respond to nutrient deprivation by decreasing global rates of transcription, translation and DNA replication. To what extent such changes can be reversed is largely unknown. We examined the effect of maternal dietary restriction on RNA synthesis in the offspring. Low protein diet fed either throughout gestation or for the preimplantation period alone reduced cellular RNA content across fetal somatic tissues during challenge and increased it beyond controls in fetal and adult tissues after challenge release. Changes in transcription of ribosomal RNA, the major component of cellular RNA, were responsible for this phenotype as evidenced by matching alterations in RNA polymerase I density and DNA methylation at ribosomal DNA loci. Cellular levels of the ribosomal transcription factor Rrn3 mirrored the rRNA expression pattern. In cell culture experiments, Rrn3 overexpression reduced rDNA methylation and increased rRNA expression; the converse occurred after inhibition of Rrn3 activity. These observations define novel mechanism where poor nutrition before implantation irreversibly alters basal rates of rRNA transcription thereafter in a process mediated by rDNA methylation and Rrn3 factor. Maternal malnutrition downregulates rDNA transcription in fetal tissues. Switch to normal diet permanently upregulates rDNA transcription compared to controls. These changes are mediated by DNA methylation and Pol I transcription factor Rrn3. This mechanism is activated before implantation.