Nuclear and mitochondrial tRNA-lookalikes in the human genome.
Nuclear and mitochondrial tRNA-lookalikes in the human genome.
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DOI：
10.3389/fgene.2014.00344
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发表时间：
2014
影响因子：
3.7
通讯作者：
Rigoutsos I
中科院分区：
文献类型：
--
作者：
Telonis AG;Loher P;Kirino Y;Rigoutsos I
我们感兴趣的是识别和表征人类基因组中含有类似于已知线粒体和核tRNA序列的位点。为此，我们使用已知的核和线粒体tRNA基因（“tRNA参考”集）来搜索“tRNA类似物”，并在不同的序列保守水平上发现了许多这样的基因座。我们发现，这些tRNA类似物中的绝大多数类似于线粒体tRNA，并表现出偏向于某些线粒体反密码子的过度代表性。我们的分析表明，tRNA类似物已经渗透到特定的染色体中，并且优先位于与已知的核tRNA非常接近的位置（z得分≤-2.54，P值≤ 0.00394）。使用公共转录本注释检查这些tRNA相似基因座的转录潜力显示，超过20%的相似基因被转录为已知蛋白质编码前mRNA、已知lncRNA或已知非蛋白质编码RNA的一部分，而公共RNA-seq数据与tRNA相似基因的终点完全一致。有趣的是，我们发现tRNA类似物在与人类健康和疾病相关的已知遗传变异中显着减少，而已知的tRNA在这些变异中富集。最后，人工比较分析了几个转录的tRNA类似物的三叶草结构，没有发现破坏性突变，这表明这些位点可能会产生功能性tRNA分子。
We are interested in identifying and characterizing loci of the human genome that harbor sequences resembling known mitochondrial and nuclear tRNAs. To this end, we used the known nuclear and mitochondrial tRNA genes (the “tRNA-Reference” set) to search for “tRNA-lookalikes” and found many such loci at different levels of sequence conservation. We find that the large majority of these tRNA-lookalikes resemble mitochondrial tRNAs and exhibit a skewed over-representation in favor of some mitochondrial anticodons. Our analysis shows that the tRNA-lookalikes have infiltrated specific chromosomes and are preferentially located in close proximity to known nuclear tRNAs (z-score ≤ −2.54, P-value ≤ 0.00394). Examination of the transcriptional potential of these tRNA-lookalike loci using public transcript annotations revealed that more than 20% of the lookalikes are transcribed as part of either known protein-coding pre-mRNAs, known lncRNAs, or known non-protein-coding RNAs, while public RNA-seq data perfectly agreed with the endpoints of tRNA-lookalikes. Interestingly, we found that tRNA-lookalikes are significantly depleted in known genetic variations associated with human health and disease whereas the known tRNAs are enriched in such variations. Lastly, a manual comparative analysis of the cloverleaf structure of several of the transcribed tRNA-lookalikes revealed no disruptive mutations suggesting the possibility that these loci give rise to functioning tRNA molecules.