Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular.
Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular.
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DOI：
10.1186/s12864-018-4660-7
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发表时间：
2018-04-20
期刊：
影响因子：
4.4
通讯作者：
Jackson MS
中科院分区：
文献类型：
--
作者：
Izuogu OG;Alhasan AA;Mellough C;Collin J;Gallon R;Hyslop J;Mastrorosa FK;Ehrmann I;Lako M;Elliott DJ;Santibanez-Koref M;Jackson MS
环状RNA（circRNA）主要来源于蛋白质编码基因，有些可以作为microRNA海绵或转录调节因子。在人类发育过程中已经确定了circRNA水平的变化，这可能在功能上很重要，但目前缺乏谱系特异性分析。为了解决这个问题，我们对向3D层压视网膜分化90天的人胚胎干（ES）细胞进行了RNAseq分析。观察到circRNA表达、大小和外显子计数在转录组范围内增加，其中circRNA水平在第45天达到平台。平行统计分析，控制样品和位点特异性效应，鉴定了239种表达变化与全转录组模式不同的circRNA，但这些都随着时间的推移而增加。令人惊讶的是，发现源自长非编码RNA（lncRNA）的circRNA比来自编码基因的circRNA占来自其起源基因座的转录物的显著更大比例。最丰富的circRMST：E12-E6在分化期间显示出> 100 X的增加，伴随着同种型转换，并且占许多成体组织中RMST转录物的> 99%。第二丰富的circFIRRE：E10-E5占分化的人ES细胞中FIRRE转录物的> 98%，并且是39种FIRRE circRNA之一，其中许多包括多个未注释的外显子。我们的研究结果表明，在人类ES细胞分化过程中，circRNA水平的变化主要是全球控制。他们还表明，RMST和FIRRE，分别在神经发生和染色体结构域的拓扑组织中具有既定作用的基因，被加工为环状lncRNA，仅具有较小的线性种类。本文的在线版本（10.1186/s12864-018-4660-7）包含补充材料，可供授权用户使用。
Circular RNAs (circRNAs) are predominantly derived from protein coding genes, and some can act as microRNA sponges or transcriptional regulators. Changes in circRNA levels have been identified during human development which may be functionally important, but lineage-specific analyses are currently lacking. To address this, we performed RNAseq analysis of human embryonic stem (ES) cells differentiated for 90 days towards 3D laminated retina. A transcriptome-wide increase in circRNA expression, size, and exon count was observed, with circRNA levels reaching a plateau by day 45. Parallel statistical analyses, controlling for sample and locus specific effects, identified 239 circRNAs with expression changes distinct from the transcriptome-wide pattern, but these all also increased in abundance over time. Surprisingly, circRNAs derived from long non-coding RNAs (lncRNAs) were found to account for a significantly larger proportion of transcripts from their loci of origin than circRNAs from coding genes. The most abundant, circRMST:E12-E6, showed a > 100X increase during differentiation accompanied by an isoform switch, and accounts for > 99% of RMST transcripts in many adult tissues. The second most abundant, circFIRRE:E10-E5, accounts for > 98% of FIRRE transcripts in differentiating human ES cells, and is one of 39 FIRRE circRNAs, many of which include multiple unannotated exons. Our results suggest that during human ES cell differentiation, changes in circRNA levels are primarily globally controlled. They also suggest that RMST and FIRRE, genes with established roles in neurogenesis and topological organisation of chromosomal domains respectively, are processed as circular lncRNAs with only minor linear species. The online version of this article (10.1186/s12864-018-4660-7) contains supplementary material, which is available to authorized users.
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影响因子：
3
作者：
Izuogu OG;Alhasan AA;Alafghani HM;Santibanez-Koref M;Elliott DJ;Jackson MS
通讯作者：
Jackson MS
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.5
作者：
Burd CE;Jeck WR;Liu Y;Sanoff HK;Wang Z;Sharpless NE
通讯作者：
Sharpless NE
影响因子：
14.9
作者：
Enuka Y;Lauriola M;Feldman ME;Sas-Chen A;Ulitsky I;Yarden Y
通讯作者：
Yarden Y
影响因子：
4.5
作者：
Barrett SP;Parker KR;Horn C;Mata M;Salzman J
通讯作者：
Salzman J