Mechanisms and Determinants of −1 Ribosome Frameshifting and Bypassing

Ribosomal frameshifting is a recoding mechanism that allows the ribosome to alter its reading frame during translation, often in response to specific messenger RNA (mRNA) elements or cellular conditions. While essential for the life cycle of many viruses, frameshifting also occurs spontaneously or in response to transfer RNA (tRNA) depletion, raising important questions about its regulation and biological relevance. This review explores the structural and kinetic principles that govern -1 frameshifting, highlighting the role of ribosome conformational dynamics, slippery sequences, and mRNA secondary structures. We discuss how programmed, hungry, and spontaneous frameshifting arise from distinct molecular pathways, yet converge on shared mechanistic features. The review also examines translational bypassing as a related form of recoding that involves large-scale ribosome sliding over noncoding regions and relies on a distinct set of RNA and ribosome conformational cues to ensure accurate take-off and landing. These insights expand our understanding of translation fidelity and recoding plasticity.