Cell-type specific features of circular RNA expression.
Cell-type specific features of circular RNA expression.
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DOI：
10.1371/journal.pgen.1003777
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Brown PO
中科院分区：
文献类型：
--
作者：
Salzman J;Chen RE;Olsen MN;Wang PL;Brown PO
人类和小鼠基因组中的数千个位点产生环状RNA转录物；在许多这些位点上，主要的RNA异构体是一个圆圈。利用一种改进的环状RNA识别计算方法，我们发现环状RNA在果蝇中广泛表达，并估计在人类中，环状RNA可能占poly(A) RNA分子数量的1%。ENCODE联盟的数据分析显示，表达环状RNA的基因库、每个基因的环状转录物与线性转录物的比例，甚至每个基因的环状RNA剪接异构体的模式都是细胞类型特异性的。这些结果表明，环状RNA的生物发生是基因表达程序中一个完整的、保守的和受调控的特征。去年，我们报道了环状RNA异构体，以前被认为是非常罕见的，实际上是真核基因表达程序的普遍特征；事实上，来自数百个人类基因的主要RNA异构体是一个圆圈。以前的新RNA物种最初似乎是特殊情况，生物学意义可疑，后来被证明具有关键的，保守的生物学作用。调控大分子的一个几乎普遍的特征是，它们在发育和分化过程中本身受到调控。在这里，我们展示了表达环状RNA的基因库，每个基因的环状线性转录物的相对水平，甚至每个基因的环状RNA的剪接异构体的模式都是细胞类型特异性的，包括惊人调节的例子。在人类中，我们估计环状RNA的分子数量约为poly(A) RNA的1%。环状RNA的普遍存在及其特异性调控可能会显著改变我们对转录后调控和RNA在细胞中发挥的作用的看法。
Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle. Using an improved computational approach for circular RNA identification, we found widespread circular RNA expression in Drosophila melanogaster and estimate that in humans, circular RNA may account for 1% as many molecules as poly(A) RNA. Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific. These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program. Last year, we reported that circular RNA isoforms, previously thought to be very rare, are actually a pervasive feature of eukaryotic gene expression programs; indeed, the major RNA isoform from hundreds of human genes is a circle. Previous novel RNA species that initially appeared to be special cases, of dubious biological significance, have subsequently proved to have critical, conserved biological roles. An almost universal characteristic of regulatory macromolecules is that they are themselves regulated during development and differentiation. Here, we show that the repertoire of genes expressing circular RNA, the relative levels of circular: linear transcripts from each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific, including examples of striking regulation. In humans, we estimate that circular RNA may account for about 1% as many molecules as poly(A) RNA. The ubiquity of circular RNA and its specific regulation could significantly alter our perspective on post-transcriptional regulation and the roles that RNA can play in the cell.