期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 20, 页码 11938-11958出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab969
关键词
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资金
- Wellcome Trust [202797/Z/16/Z, 203864/Z/16/Z, 106207]
- Sir Henry Dale fellowship from the Wellcome Trust [098406/Z/12/B, 221818/Z/20/Z]
- Royal Society
- European Research Council [646891]
- Helmholtz Association
- European Research Council StG [948636]
- European Research Council (ERC) [948636] Funding Source: European Research Council (ERC)
- Wellcome Trust [203864/Z/16/Z, 202797/Z/16/Z, 221818/Z/20/Z] Funding Source: Wellcome Trust
The 2A protein of TMEV stimulates PRF during infection by recognizing RNA elements and forming pseudoknots. Experiments using disome analysis identified ribosome stacking at the TMEV frameshifting signal.
The 2A protein of Theiler's murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed -1 ribosomal frameshifting (PRF) during infection. Here, we present the X-ray crystal structure of TMEV 2A and define how it recognises the stimulatory RNA element. We demonstrate a critical role for bases upstream of the originally predicted stem-loop, providing evidence for a pseudoknot-like conformation and suggesting that the recognition of this pseudoknot by beta-shell proteins is a conserved feature in cardioviruses. Through examination of PRF in TMEV-infected cells by ribosome profiling, we identify a series of ribosomal pauses around the site of PRF induced by the 2A-pseudoknot complex. Careful normalisation of ribosomal profiling data with a 2A knockout virus facilitated the identification, through disome analysis, of ribosome stacking at the TMEV frameshifting signal. These experiments provide unparalleled detail of the molecular mechanisms underpinning Theilovirus protein-stimulated frameshifting.
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