Noncoding RNAs orchestrating the central dogma.
Sebastian Lozano-Villada, Sathyanarayanan V Puthanveettil
Abstract
Open AccessOnce considered mere transcriptional noise, noncoding RNAs (ncRNAs) are now recognized as central players in cellular function-serving as scaffolds, catalysts, and regulators of gene expression. Their pervasive influence compelled a fundamental reevaluation of the central dogma of molecular biology, which traditionally emphasized the linear flow of genetic information from DNA to RNA to protein. In this review, we highlight critical roles played by ncRNAs and the outstanding challenges in decoding their mechanisms of action. We focus in particular on the emergent view that ncRNAs operate as components of highly integrated and dynamic regulatory networks. These RNA interactomes are governed by precise spatiotemporal constraints yet remain flexible enough to adapt to shifting cellular demands. Key questions remain about how such networks are prioritized, regulated, and dynamically reshaped in response to physiological signals. To contextualize these mechanisms, we spotlight the nervous system, a tissue enriched in regulatory RNAs, as a model for understanding how ncRNA-mediated regulation contributes to cellular specialization and plasticity. Unraveling the principles governing ncRNA interactions will reveal new dimensions of the genetic code, one that is not simply read but interpreted and orchestrated by RNA.