Course Content
CPBP 8328 | QSBC Seminar Series
About Lesson

Long noncoding RNAs (LncRNAs) are increasingly recognized as being involved in human physiology and diseases, but there is a lack of mechanistic understanding for the majority of lncRNAs. We comparatively tested proposed mechanisms of antisense lncRNA regulation at the X-chromosome Inactivation (XCI) locus. Our single-cell analyses argue against mechanisms that require the Xist or Tsix transcript to bind to each other. Intriguingly, we find that due to stochasticity in transcription, different mechanisms based on the act of transcription regulate Xist and Tsix at different levels of nascent transcription. At medium levels, RNA polymerases transcribe Xist and Tsix on each strand at the same transcription site and deposit significant amounts of the histone mark H3K36me3, which inhibits Xist. At high levels of nascent transcription, many RNA polymerases transcribe Xist or Tsix resulting in transcriptional interference. Therefore, lncRNA expression variability is not just a quirk of transcription but an important aspect of regulation that allows multiple mechanisms to be employed by the same gene locus within the same cell population.

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