Pluto Bioinformatics

GSE89957: Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular

Bulk RNA sequencing

Circular RNAs (circRNAs) are numerically abundant in human, predominantly derived from protein coding genes, and some can act as microRNA sponges or cis-acting transcriptional regulators. Changes in circRNA abundance 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 abundance, size, and exon count was observed which reached a plateau by day 45. Parallel analyses, controlling for sample and locus specific effects, identified 239 circRNAs with expression patterns distinct from the transcriptome-wide pattern, but these 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 which was associated with altered promoter usage, 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 abundance are primarily globally controlled. They also suggest that RMST and FIRRE, genes with established roles in neurogenesis and topological organisation of chromosomal domains respectively, encode circular lncRNAs with only minor linear species. SOURCE: Michael Jackson ( - Institute of Genetic Medicine

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