Single cell analysis of developing Merkel cells reveals the emergence of non-coding RNA biotypes as a hallmark of...

RNA processing generates diverse protein-coding and non-coding transcripts, yet RNA biotype diversity during cellular differentiation is not well characterized. Merkel cells (MCs) are cutaneous mechanosensors. We analyzed full-length transcripts of FACS-sorted single mouse MCs at all stages of development and discovered that their terminal differentiation was accompanied by an emergence of non-coding transcripts associated with genes related to MC function. Non-coding RNAs upregulated during terminal differentiation included retained intron transcripts capable of forming nuclear condensates that contained their cognate mRNAs. We showed that Aspa retained intron condensates prevented the nuclear export of Aspa mRNA, reducing ASPA expression. Transcripts associated with terminal differentiation in five other mammalian cell types also showed an increased abundance of non-coding biotypes and this was attenuated in differentiation-defective Down syndrome neurons. These findings strongly suggest that the emergence of non-coding transcripts is a general feature of terminal differentiation and retained intron condensates can function to regulate gene expression.