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bioRxiv · 10.1101/2021.08.25.457323

High temporal resolution RNA-seq time course data reveals mammalian lncRNA activationmirrors neighbouring protein-coding genes

Muskovic, W.·Slavich, E.·Maslen, B.·Kaczorowski, D.·Cursons, J.·Crampin, E.·Kavallaris, M.
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Abstract

BackgroundThe advent of next-generation sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long non-coding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Compellingly, lncRNA expression is strongly linked with adjacent protein-coding gene expression, suggesting a potential cis-regulatory function. Evidence for these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes. ResultsWhere causal cis-regulatory relationships exist, lncRNA activation is expected to precede changes in adjacent target gene expression. Using an RNA-seq time course of uniquely high temporal resolution, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings reveal lncRNAs are expressed synchronously with adjacent protein-coding genes. Analysis of lipopolysaccharide-activated mouse dendritic cells revealed the same temporal relationship observed in transitioning human cells. ConclusionOur findings suggest broad-scale cis-regulatory roles for lncRNAs are not common. The strong association between lncRNAs and adjacent genes may instead indicate an origin as transcriptional by-products from active protein-coding gene promoters and enhancers.

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Muskovic, W., Slavich, E., Maslen, B., Kaczorowski, D., Cursons, J., Crampin, E., Kavallaris, M.. 2021-08-26. High temporal resolution RNA-seq time course data reveals mammalian lncRNA activationmirrors neighbouring protein-coding genes. https://doi.org/10.1101/2021.08.25.457323

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