The lncRNA HOTAIR is the most differentially expressed gene between upper- and lower-body adipose tissue, but its significance in adipogenesis is unclear. We report that HOTAIR expression is transiently induced during early adipogenic differentiation of gluteofemoral adipose progenitors and is repressed in mature adipocytes. Upon adipogenic commitment, HOTAIR regulates protein synthesis pathways and cytoskeleton remodeling with a later impact on adipocyte lipid storage capacity. Our results support novel and important functions of HOTAIR in the physiological context of adipogenesis.
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. Using a capture long-read sequencing approach, we characterize HOTAIR isoforms expressed in human primary adipose stem cells. We find HOTAIR isoforms population displays varied splicing patterns, frequently leading to the exclusion or truncation of canonical LSD1 and PRC2 binding domains. We identify a highly cell type-specific HOTAIR isoform pool regulated by distinct promoter usage, and uncover a shift in the HOTAIR TSS usage that modulates the balance of HOTAIR isoforms at differentiation onset. 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.
Potolitsyna et al. Long non-coding RNA HOTAIR regulates cytoskeleton remodeling and lipid storage capacity during adipogenesis. 2022. Sci Rep. 12:10157 https://pubmed.ncbi.nlm.nih.gov/35710716/
Potolitsyna et al. De novo annotation of lncRNA HOTAIR transcripts by long-read RNA capture-seq reveals a differentiation-driven isoform switch. 2022. BMC Genomics 23, 658 https://pubmed.ncbi.nlm.nih.gov/36115964/
