Pseudo-messenger RNA: phantoms of the transcriptome.
Pseudo-messenger RNA: phantoms of the transcriptome.
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DOI：
10.1371/journal.pgen.0020023
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发表时间：
2006-04
期刊：
影响因子：
4.5
通讯作者：
Huminiecki L
中科院分区：
文献类型：
--
作者：
Frith MC;Wilming LG;Forrest A;Kawaji H;Tan SL;Wahlestedt C;Bajic VB;Kai C;Kawai J;Carninci P;Hayashizaki Y;Bailey TL;Huminiecki L
哺乳动物转录组包含一些难以分类和分析的模糊实体。与假基因类似，我们将假信使RNA定义为类似于编码蛋白质的mRNA，但由于阅读框中断而无法编码全长蛋白质的RNA分子。通过一个严格的计算流程（排除了测序错误），我们在102801个FANTOM3小鼠cDNA中鉴定出10679个假信使RNA（其中约一半与转座子相关）：占FANTOM3转录组的略多于10%。这些不仅包括转录的假基因，还包括原本编码蛋白质的基因的剪接变体中断情况。有些可能编码截短的蛋白质，其中只有少数似乎受到无义介导的衰变影响。存在大量仅因出现opal终止密码子而中断的转录本，这表明硒蛋白的数量比目前估计的要多。我们还描述了补偿性移码，即基因的一个片段改变了阅读框但仍可翻译。总之，我们研究了一大类非标准但可能具有功能的转录本，它们可能以新的方式编码遗传信息并影响生物过程。这些转录本中的许多并不能与基因组中任何可识别的对象完全对应，这意味着在基因组序列水平上注释所有功能元件的目标存在根本限制。
我们对遗传学的理解一直被所谓的中心法则所主导：即DNA转录为RNA，RNA通过遗传密码翻译产生蛋白质的理论。因此，DNA是遗传信息的遗传储存库，蛋白质是执行细胞功能的最终产物，而RNA是一种被动的中间产物，因此被称为信使RNA。然而，越来越多的证据表明RNA所起的作用比这要动态得多。这项研究对“病态”RNA分子进行了无偏见的研究，这些分子类似于编码蛋白质的RNA，只是它们包含违反遗传密码的情况。这些假信使RNA在所有转录本中所占比例惊人地高，多达10%。这些幽灵般的分子一直在RNA研究中存在，但一直未被关注，因为它们与DNA中的注释元素（即“基因”）并不完全对应。它们的普遍存在表明RNA是一个独特的领域，不能仅仅作为DNA或蛋白质的镜像来完全理解。
The mammalian transcriptome harbours shadowy entities that resist classification and analysis. In analogy with pseudogenes, we define pseudo–messenger RNA to be RNA molecules that resemble protein-coding mRNA, but cannot encode full-length proteins owing to disruptions of the reading frame. Using a rigorous computational pipeline, which rules out sequencing errors, we identify 10,679 pseudo–messenger RNAs (approximately half of which are transposon-associated) among the 102,801 FANTOM3 mouse cDNAs: just over 10% of the FANTOM3 transcriptome. These comprise not only transcribed pseudogenes, but also disrupted splice variants of otherwise protein-coding genes. Some may encode truncated proteins, only a minority of which appear subject to nonsense-mediated decay. The presence of an excess of transcripts whose only disruptions are opal stop codons suggests that there are more selenoproteins than currently estimated. We also describe compensatory frameshifts, where a segment of the gene has changed frame but remains translatable. In summary, we survey a large class of non-standard but potentially functional transcripts that are likely to encode genetic information and effect biological processes in novel ways. Many of these transcripts do not correspond cleanly to any identifiable object in the genome, implying fundamental limits to the goal of annotating all functional elements at the genome sequence level. Our understanding of genetics has been dominated by the so-called central dogma: the theory that DNA is transcribed into RNA, which is translated via the genetic code to produce proteins. Thus, DNA is the inherited store of genetic information, proteins are the end products that carry out cellular functions, and RNA is a kind of passive intermediary, hence termed messenger RNA. However, evidence has been accumulating that RNA plays a much more dynamic role than this. This study provides an unprejudiced survey of “pathological” RNA molecules, which resemble protein-coding RNA except that they contain violations of the genetic code. These pseudo–messenger RNAs constitute a surprisingly large fraction of all transcripts, as much as 10%. These ghostly molecules have always been present in RNA surveys, but have stayed below the radar because they do not cleanly correspond to annotated elements in DNA, i.e., “genes”. Their prevalence demonstrates that RNA is a distinct continent that cannot be fully understood as a mirror of DNA or proteins.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
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56.9
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