Abstract
BackgroundA significant portion of expressed non-coding RNAs in human cells is derived from transposable elements (TEs). Moreover, it has been shown that various long non-coding RNAs (lncRNAs), which come from the human endogenous retrovirus subfamily H (HERVH), are not only expressed but required for pluripotency in human embryonic stem cells (hESCs).ResultsTo identify additional TE-derived functional non-coding transcripts, we generated RNA-seq data from induced pluripotent stem cells (iPSCs) of four primate species (human, chimpanzee, gorilla, and rhesus) and searched for transcripts whose expression was conserved. We observed that about 30% of TE instances expressed in human iPSCs had orthologous TE instances that were also expressed in chimpanzee and gorilla. Notably, our analysis revealed a number of repeat families with highly conserved expression profiles including HERVH but also MER53, which is known to be the source of a placental-specific family of microRNAs (miRNAs). We also identified a number of repeat families from all classes of TEs, including MLT1-type and Tigger families, that contributed a significant amount of sequence to primate lncRNAs whose expression was conserved.ConclusionsTogether, these results describe TE families and TE-derived lncRNAs whose conserved expression patterns can be used to identify what are likely functional TE-derived non-coding transcripts in primate iPSCs.
Highlights
A significant portion of expressed non-coding RNAs in human cells is derived from transposable elements (TEs)
One example of a TE-derived Long non-coding RNA (lncRNA) is lnc-RoR, a transcript implicated in the modulation of reprogramming of human induced pluripotent stem cells (iPSCs) [9], which initiates in the human endogenous retrovirus subtype H (HERVH) [7]
Overall we found that more than 90% of repeat instances across all major repeat families were conserved between human and chimpanzee or gorilla, about 85% were conserved in rhesus and over 80% were conserved across all analyzed primate species (Fig. 1a)
Summary
A significant portion of expressed non-coding RNAs in human cells is derived from transposable elements (TEs). It has been shown that various long non-coding RNAs (lncRNAs), which come from the human endogenous retrovirus subfamily H (HERVH), are expressed but required for pluripotency in human embryonic stem cells (hESCs). It has been shown that an important source of lncRNA sequences are transposable elements (TEs), which make up about 50% of the human genome [6]. It was shown that the expression of these TE-derived lncRNA transcripts helps define the naive stem-cell state [13] and knockdown experiments confirmed that this expression is essential for the maintenance of pluripotency in human stem cells [14]. HERVH-derived lncRNAs are probably not the only TEderived transcripts involved in stem cell pluripotency, as knockdowns of several lncRNAs result in exit from the pluripotent state [15]
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