From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation

The functional characterization of long non-coding RNAs (lncRNA) has been disproportionately shaped by the paradigm of cytoplasmic miRNA sponging, a model that, while valid for many transcripts, has overshadowed a more fundamental and impactful role. This opinion article argues for a critical conceptual shift, positing that the most potent role of many lncRNAs is not as competitive sponges, but as primary architects and scaffolds of the epigenetic landscape. The prevailing focus on the cytoplasm has created diagnostic and therapeutic blind spots. We contend that deliberately recentering the narrative around lncRNAs as nuclear scaffolds and specificity factors for chromatin-modifying complexes is essential for identifying precise disease biomarkers and developing the next generation of targeted epigenetic therapies.