A New Perspective on Information Transfer from Proteins to Nucleic Acids

Francis Crick proposed the Central Dogma in 1958, stating the unidirectional flow of genetic information from DNA to protein. However, subsequent discoveries have progressively revised and expanded this paradigm. The discovery of reverse transcriptase demonstrated that information can flow from RNA back to DNA, contradicting the original unidirectional formulation. Although there is currently no definitive evidence demonstrating the reverse regulation of nucleic acids by proteins, recent studies appear to challenge the concept of irreversible information flow from nucleic acids to proteins. The defense-associated reverse transcriptases (DRTs), through their specific structural domains, can manipulate the formation of specific nucleic acid sequences, revealing a protein-template-based mechanism for sequence-specific DNA synthesis. This review summarizes the potential mechanisms by which proteins regulate nucleic acid formation. More broadly, proteins, acting as transcription factors, RNA-binding proteins (RBPs), or undergoing specific post-translational modifications (PTMs), participate in epigenetic regulation or RNA editing, ultimately enabling feedback or feedforward regulation of their own nucleic acid counterparts. These findings are insufficient to overturn the core principle of the Central Dogma, but they provide a new perspective on information flow from proteins to nucleic acids, and offer novel insights into intracellular information transmission and the potential mechanisms underlying disease development.