Retinoic Acid and Long Noncoding RNAs Crosstalk: Implications for Neuronal Differentiation and Diseases

Retinoic acid (RA), a biologically active metabolite of vitamin A, acts as a potent signaling molecule regulating cell proliferation, differentiation, and apoptosis through nuclear RA receptors. RA influences expression of multiple genes, which are essential for development, neuronal differentiation, and synaptic plasticity. Long noncoding RNAs (lncRNAs), a class of regulatory RNAs, influence gene expression through chromatin organization, RNA processing and stability, translation, miRNA dynamics, and can also encode micropeptides. This review emphasizes the RA-mediated modulation of lncRNA expression through transcriptional and post-transcriptional mechanisms that influence differentiation and cell fate. This intricate RA-lncRNA crosstalk shapes tissue development and underlies the molecular pathology of various diseases. Both RA-signaling and lncRNA networks are involved in aging and age-related diseases. Furthermore, emerging RNA-based therapeutics such as RNA aptamers, RNA interference, and CRISPR-guided RNAs highlight their promise for treating age-related diseases. Exploring the crosstalk between RA and lncRNAs may provide novel opportunities for RNA-based therapeutic interventions targeting various diseases.