Role of lncRNAs related to NRs in the regulation of gene expression

Long non-coding RNAs (lncRNAs) play a key role in regulating gene expression, influencing various cellular pathways by interacting with transcription factors, other RNA molecules like miRNAs, and DNA. In this study, we focused on the role of lncRNAs related to nuclear receptors (NRs), which are a family of transcription factors activated by ligands. NRs are involved in vital biological processes such as metabolism, immune response, reproduction, and development. We discovered six novel sequence motifs within lncRNAs that respond to multiple NRs suggesting they are not specific to a single receptor. One of the motifs, was complementary to miRNA hsa-miR-1908-3p, suggesting that lncRNAs containing this motif may function as miRNA sponges, regulating the expression of about 487 target mRNAs. The motifs were also found in key regulatory regions of the human genome, particularly on chromosome 19, including in Adeno-associated virus integration site 1 (AAVS1), a region with a high regulatory role in gene expression. Additionally, an evolutionary analysis was conducted revealing that these motifs are highly conserved across species, including Mus musculus, Euglena gracilis, and Saccharomyces cerevisiae, indicating their ancient origins. Based on these results, we propose that these motifs may represent ancestral binding sites for nuclear receptor precursors, and may act as backup mechanisms in modern organisms, ensuring the functional versatility and evolutionary conservation of NR-mediated gene regulation.