Possible formation of mitochondrial-RNA containing chimeric or trimeric RNA implies a post-transcriptional and post-splicing mechanism for RNA fusion.

Possible formation of mitochondrial-RNA containing chimeric or trimeric RNA implies a post-transcriptional and post-splicing mechanism for RNA fusion.
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DOI:
10.1371/journal.pone.0077016
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Liao DJ
Liao DJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yang W;Wu JM;Bi AD;Ou-Yang YC;Shen HH;Chirn GW;Zhou JH;Weiss E;Holman EP;Liao DJ

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已知人类细胞表达许多嵌合rna,即含有两个基因序列的rna。我们想知道是否也存在三聚体RNA,即含有三个基因序列的RNA,我们编写了简单的计算机代码筛选了储存在不同公共数据库中的人类表达序列标签(human expression sequence tags, ESTs),并获得了数百个推测的三聚体est。利用NCBI Blast和UCSC Blat浏览器对其序列进行进一步分析,鉴定出61条三聚体EST和2条四聚体EST(1条EST包含4条不同的序列)。我们还鉴定了57种嵌合、三聚体或四聚体est,它们同时含有线粒体(mt) RNA和核RNA (nRNA),即mtRNA-nRNA融合。在一些三聚体est中,下游伙伴被融合到上游伙伴的poly-A尾部,这与mtRNA-nRNA融合一起,表明可能存在一种新的RNA融合机制,这种机制发生在转录和剪接终止之后,可能发生在核外,而不是目前假设的两种机制,即反式剪接和转录滑移,发生在核内。mtRNA-nRNA融合体中的mt-序列在细胞核中有假基因,但令人惊讶的是,主要定位在1号和5号染色体上。在一些mtRNA- nrna融合中,以及在一些仅由mtRNA衍生的ESTs中,mt序列可能是顺式或反式剪接。实际上,我们克隆了一个新的顺式拼接mtRNA,命名为16SrRNA-s。因此,mtDNA可能并不总是缺少内含子。三种或多种RNA融合为一种,nRNA与mtRNA融合,以及mtRNA的顺式或反式剪接都应该扩大细胞RNA库,从而扩大细胞功能。因此,未来对这些新型融合rna和剪接mtrna在人类细胞中存在的实验验证将显著促进我们对生物学和医学的理解。
Human cells are known to express many chimeric RNAs, i.e. RNAs containing two genes' sequences. Wondering whether there also is trimeric RNA, i.e. an RNA containing three genes' sequences, we wrote simple computer code to screen human expression sequence tags (ESTs) deposited in different public databases, and obtained hundreds of putative trimeric ESTs. We then used NCBI Blast and UCSC Blat browsers to further analyze their sequences, and identified 61 trimeric and two tetrameric ESTs (one EST containing four different sequences). We also identified 57 chimeric, trimeric or teterameric ESTs that contained both mitochondrial (mt) RNA and nuclear RNA (nRNA), i.e. were mtRNA-nRNA fusions. In some trimeric ESTs, the downstream partner was fused to the poly-A tail of the upstream partner, which, together with the mtRNA-nRNA fusions, suggests a possible new mechanism for RNA fusion that occurs after both transcription and splicing have been terminated, and possibly outside the nucleus, in contrast to the two current hypothetical mechanisms, trans-splicing and transcriptional-slippage, that occur in the nucleus. The mt-sequences in the mtRNA-nRNA fusions had pseudogenes in the nucleus but, surprisingly, localized mainly in chromosomes 1 and 5. In some mtRNA-nRNA fusions, as well as in some ESTs that were derived only from mtRNA, the mt-sequences might be cis- or trans-spliced. Actually, we cloned a new cis-spliced mtRNA, coined as 16SrRNA-s. Hence, mtDNA may not always be intron-less. Fusion of three or more RNAs to one, fusion of nRNA to mtRNA, and cis- or trans-splicing of mtRNA should all enlarge the cellular RNA repertoire, in turn enlarging the cellular functions. Therefore, future experimental verification of the existence of these novel classes of fusion RNAs and spliced mtRNAs in human cells should significantly advance our understanding of biology and medicine.
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