High temporal resolution RNA-seq time course data reveals widespread synchronous activation between mammalian lncRNAs and neighboring protein-coding genes.
Walter Muskovic, Eve Slavich, Ben Maslen, Dominik C Kaczorowski, Joseph Cursons, Edmund Crampin, Maria Kavallaris
Author Information
Walter Muskovic: Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia. ORCID
Eve Slavich: Stats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, New South Wales 2052, Australia. ORCID
Ben Maslen: Stats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, New South Wales 2052, Australia. ORCID
Dominik C Kaczorowski: Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia. ORCID
Joseph Cursons: The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia. ORCID
Edmund Crampin: Systems Biology Laboratory, School of Mathematics and Statistics and Department of Biomedical Engineering, University of Melbourne, Victoria 3010, Australia. ORCID
Maria Kavallaris: Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia. ORCID
The advent of massively parallel sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long noncoding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Expression of lncRNAs is strongly linked with adjacent protein-coding gene expression, suggesting potential -regulatory functions. A more detailed understanding of these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes. Despite the diversity of reported lncRNA regulatory mechanisms, where causal -regulatory relationships exist, lncRNA transcription is expected to precede changes in target gene expression. Using a high temporal resolution RNA-seq time course, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings reveal that 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. Our findings suggest broad-scale -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.
