Abstract

Forty years after the term 'RNA world' was coined, the RNA world hypothesis is best framed as an RNA-centered evolutionary phase rather than as an RNA-only biosphere. Recent advances in systems chemistry now turn several long-standing objections into experimentally measurable constraints. These include linking nucleotide activation with template copying, quantifying how wet-dry cycling and freeze-thaw cycles alter polymer growth, and testing how compartments change retention, exchange, and parasite control. In parallel, polymerase ribozymes now connect structure, processivity, fidelity, and sustained RNA-catalyzed evolution. Peptide ligation in water, thioester-mediated aminoacyl-RNA chemistry, peptidyl-RNA synthesis, and peptide effects on RNA folding support ribonucleoprotein models in which peptides are integrated partners in a coevolutionary process. Remaining bottlenecks define testable benchmarks in chemically heterogeneous RNA-centered systems.