The lncRNA EPB41L4A-AS1 regulates gene expression in the nucleus and exerts cell type-dependent effects on cell cycle progression

Abstract

The long non-coding RNA (lncRNA) EPB41L4A-AS1 is aberrantly expressed in various cancers and has been reported to be involved in metabolic reprogramming and as a repressor of the Warburg effect. Although the biological relevance of EPB41L4A-AS1 is evident, its functional role seems to vary depending on cell type and state of disease. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we previously identified EPB41L4A-AS1 to be one of 59 lncRNAs with potential cell cycle functions. Here, we demonstrate that EPB41L4A-AS1 exists as bright foci and regulates gene expression in the nucleus in both cis and trans. Specifically, we find that EPB41L4A-AS1 positively regulates its sense overlapping gene EPB41L4A and influences expression of hundreds of other genes, including genes involved in cell proliferation. Finally, we show that EPB41L4A-AS1 affects cell cycle phase distribution, though these effects vary between cell types.