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bioRxiv · 10.1101/2022.06.17.496514

De novo annotation of lncRNA HOTAIR transcripts by long-read RNA capture-seq reveals a differentiation-driven isoform switch

Potolitsyna, E.·Hazell Pickering, S.·Tooming-Klunderud, A.·Collas, P.·Briand, N.
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Abstract

BackgroundLncRNAs are tissue-specific and emerge as important regulators of various biological processes and as disease biomarkers. HOTAIR is a well-established pro-oncogenic lncRNA which has been attributed a variety of functions in cancer and native contexts. However, a lack of an exhaustive, cell type-specific annotation questions whether HOTAIR functions are supported by the expression of multiple isoforms. ResultsUsing a capture long-read sequencing approach, we characterize HOTAIR isoforms expressed in human primary adipose stem cells. We identify a highly cell type-specific HOTAIR isoform and uncover a shift in the HOTAIR isoform balance at differentiation onset. Composition of the HOTAIR isoform pool is regulated by distinct promoter usage and is under control of hormonal and nutrient-sensing pathways. ConclusionOur results highlight the complexity and cell type-specificity of HOTAIR isoforms and open perspectives on functional implications of these variants and their balance to key cellular processes.

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Potolitsyna, E., Hazell Pickering, S., Tooming-Klunderud, A., Collas, P., Briand, N.. 2022-06-17. De novo annotation of lncRNA HOTAIR transcripts by long-read RNA capture-seq reveals a differentiation-driven isoform switch. https://doi.org/10.1101/2022.06.17.496514

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