Transposable Element-Gene Splicing Modulates the Transcriptional Landscape of Human Pluripotent Stem Cells
Babarinde, I. A.; Ma, G.; Li, Y.; Deng, B.; Luo, Z.; Liu, H.; Abdul, M.; Ward, C.; Chen, M.; Fu, X.; Duttlinger, M.; He, J.; Sun, L.; Li, W.; Zhuang, Q.; Frampton, J.; Cazier, J.-B.; Chen, J.; Jauch, R.; Esteban, M. A.; Hutchins, A.
Show abstract
Transposable elements (TEs) occupy nearly 50% of mammalian genomes and are both potential dangers to genome stability and functional genetic elements. TEs can be expressed and exonised as part of a transcript, however, their full contribution to the transcript splicing remains unresolved. Here, guided by long and short read sequencing of RNAs, we show that 26% of coding and 65% of non-coding transcripts of human pluripotent stem cells (hPSCs) contain TEs. Different TE families have unique integration patterns with diverse consequences on RNA expression and function. We identify hPSC-specific splicing of endogenous retroviruses (ERVs) as well as LINE L1 elements into protein coding genes that generate TE-derived peptides. Finally, single cell RNA-seq reveals that proliferating hPSCs are dominated by ERV-containing transcripts, and subpopulations express SINE or LINE-containing transcripts. Overall, we demonstrate that TE splicing modulates the pluripotency transcriptome by enhancing and impairing transcript expression and generating novel transcripts and peptides.
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