The RNA Revolution in the Central Molecular Biology Dogma Evolution

Abstract

Human genome projects in the 1990s identified about 20,000 protein-coding sequences. We are now in the RNA revolution, propelled by the realization that genes determine phenotype beyond the foundational central molecular biology dogma, stating that inherited linear pieces of DNA are transcribed to RNAs and translated into proteins. Crucially, over 95% of the genome, initially considered junk DNA between protein-coding genes, encodes essential, functionally diverse non-protein-coding RNAs, raising the gene count by at least one order of magnitude. Most inherited phenotype-determining changes in DNA are in regulatory areas that control RNA and regulatory sequences. RNAs can directly or indirectly determine phenotypes by regulating protein and RNA function, transferring information within and between organisms, and generating DNA. RNAs also exhibit high structural, functional, and biomolecular interaction plasticity and are modified via editing, methylation, glycosylation, and other mechanisms, which bestow them with diverse intra- and extracellular functions without altering the underlying DNA. RNA is, therefore, currently considered the primary determinant of cellular to populational functional diversity, disease-linked and biomolecular structural variations, and cell function regulation. As demonstrated by RNA-based coronavirus vaccines’ success, RNA technology is transforming medicine, agriculture, and industry, as did the advent of recombinant DNA technology in the 1980s.