Genome-wide survey of interindividual differences of RNA stability in human lymphoblastoid cell lines.

Genome-wide survey of interindividual differences of RNA stability in human lymphoblastoid cell lines.
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人淋巴母细胞系中RNA稳定性的个体稳定性差异的全基因组调查。

DOI:
10.1038/srep01318
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Gejman, Pablo V.
Gejman, Pablo V.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Duan, Jubao;Shi, Jianxin;Ge, Xijin;Doelken, Lars;Moy, Winton;He, Deli;Shi, Sandra;Sanders, Alan R.;Ross, Jeff;Gejman, Pablo V.

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RNA稳定性在个体之间的差异程度及其对个体间表达变异的贡献仍然未知。我们在7个人类HapMap淋巴母细胞样细胞系(LCL)中进行了RNA稳定性的全基因组分析,并分析了DNA序列变异对RNA半衰期差异的影响。26%的表达基因在LCL之间表现出RNA半衰期差异,错误发现率(FDR)< 0.05,这占个体之间基因表达差异的约37%。无义多态性与RNA半衰期缩短相关。在呈现个体间RNA半衰期差异的基因中,较高的编码GC 3含量(第三密码子位置的G和C百分比)与RNA半衰期增加相关。一致的是,G和C等位基因的单核苷酸多态性(SNPs)的蛋白质编码序列与增强RNA的稳定性。这些结果表明,广泛的个体间差异,RNA的稳定性相关的DNA序列和组成的变化。
The extent to which RNA stability differs between individuals and its contribution to the interindividual expression variation remain unknown. We conducted a genome-wide analysis of RNA stability in seven human HapMap lymphoblastoid cell lines (LCLs) and analyzed the effect of DNA sequence variation on RNA half-life differences. Twenty-six percent of the expressed genes exhibited RNA half-life differences between LCLs at a false discovery rate (FDR) < 0.05, which accounted for ~ 37% of the gene expression differences between individuals. Nonsense polymorphisms were associated with reduced RNA half-lives. In genes presenting interindividual RNA half-life differences, higher coding GC3 contents (G and C percentages at the third-codon positions) were correlated with increased RNA half-life. Consistently, G and C alleles of single nucleotide polymorphisms (SNPs) in protein coding sequences were associated with enhanced RNA stability. These results suggest widespread interindividual differences in RNA stability related to DNA sequence and composition variation.
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