Heterogeneous and multiple conformational transition pathways between pseudoknots of the SARS-CoV-2 frameshift element.

ABSTRACT: Frameshifting is an essential mechanism employed by many viruses including coronaviruses to produce viral proteins from a compact RNA genome. It is facilitated by specific RNA folds in the frameshift element (FSE), which has emerged as an important therapeutic target. For SARS-CoV-2, a specific 3-stem pseudoknot has been identified to stimulate frameshifting. However, prior studies and our RNA-As-Graphs analysis coupled to chemical reactivity experiments revealed other folds, including a different pseudoknot. Although structural plasticity has been proposed to play a key role in frameshifting, paths between different FSE RNA folds have not been yet identified. Here, we capture atomic-level transition pathways between two key FSE pseudoknots by transition path sampling coupled to Markov Sta

SUBMITTER: Yan S 

PROVIDER: S-EPMC11789066 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature