Diversity of human tRNA genes from the 1000-genomes project
Diversity of human tRNA genes from the 1000-genomes project
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DOI：
10.4161/rna.27361
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发表时间：
2013-12-01
期刊：
影响因子：
4.1
通讯作者：
Pan, Tao
中科院分区：
文献类型：
--
作者：
Parisien, Marc;Wang, Xiaoyun;Pan, Tao
人类个体基因组的序列多样性已被广泛分析，以了解 mRNA、miRNA 和长非编码 RNA 基因的变异和表型影响。 TRNA (tRNA) 在人类基因组中也表现出巨大的序列多样性，但 tRNA 基因序列变异和对个体人类基因组的潜在功能影响尚未得到研究。在这里，我们利用千基因组计划的测序数据来检查人群中 tRNA 基因的多样性。先前对参考人类基因组的分析表明，存在超出翻译必要性的大量不同 tRNA 基因，这表明某些 tRNA 转录本可能执行非规范功能。我们在 > 1% 的个体中发现了 24 个新的 tRNA 序列，在 > 0.2% 的个体中发现了 76 个新的 tRNA 序列，这表明 tRNA 基因也受到人类群体进化变化的影响。出乎意料的是，两个丰富的新 tRNA 基因在反密码子茎中含有碱基对错配。我们通过实验确定这两种新的 tRNA 在体外发生了结构改变；然而，一种新的 tRNA 并未被氨酰化，但在 HeLa 细胞中极其稳定，这表明这种新的 tRNA 可用于非规范功能。我们的结果表明，在人口规模上，tRNA 基因比传统理解的更加多样化，并且一些新的 tRNA 可能执行与人类健康和疾病相关的非规范、翻译外功能。
The sequence diversity of individual human genomes has been extensively analyzed for variations and phenotypic implications for mRNA, miRNA, and long non-coding RNA genes. TRNA (tRNA) also exhibits large sequence diversity in the human genome, but tRNA gene sequence variation and potential functional implications in individual human genomes have not been investigated. Here we capitalize on the sequencing data from the 1000-genomes project to examine the diversity of tRNA genes in the human population. Previous analysis of the reference human genome indicated an unexpected large number of diverse tRNA genes beyond the necessity of translation, suggesting that some tRNA transcripts may perform non-canonical functions. We found 24 new tRNA sequences in > 1% and 76 new tRNA sequences in > 0.2% of all individuals, indicating that tRNA genes are also subject to evolutionary changes in the human population. Unexpectedly, two abundant new tRNA genes contain base-pair mismatches in the anticodon stem. We experimentally determined that these two new tRNAs have altered structures in vitro; however, one new tRNA is not aminoacylated but extremely stable in HeLa cells, suggesting that this new tRNA can be used for non-canonical function. Our results show that at the scale of human population, tRNA genes are more diverse than conventionally understood, and some new tRNAs may perform non-canonical, extra-translational functions that may be linked to human health and disease.