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Preprints

De novoannotation of lncRNAHOTAIRtranscripts by long-read RNA capture-seq reveals a differentiation-driven isoform switch

Potolitsyna E, Pickering SH, Tooming-Klunderud A, Collas P, Briand N.
Preprint from
bioRxiv
17 June 2022
PPR
PPR507017
Abstract

Background

LncRNAs 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.

Results

Using 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.

Conclusion

Our 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.