國家衛生研究院 NHRI:Item 3990099045/15552
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    题名: Programmable modulation of ribosomal frameshifting by mRNA targeting CRISPR-Cas12a system
    作者: Huang, SH;Chen, SC;Wu, TY;Chen, CY;Yu, CH
    贡献者: National Institute of Cancer Research
    摘要: Minus 1 programmed ribosomal frameshifting (−1 PRF) is a conserved translational regulation event essential for critical biological processes, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Efficient trans-modulation of the structured RNA element crucial to −1 PRF will endow the therapeutic application. Here, we demonstrate that CRISPR RNA can stimulate efficient −1 PRF. Assembled CRISPR-Cas12a, but not CRISPR-Cas9, complex further enhances −1 PRF efficiency through its higher capacity to stall translating ribosomes. We additionally perform CRISPR-Cas12a targeting to impair the SARS-CoV-2 frameshifting pseudoknot structure via a focused screening. We demonstrate that targeting CRISPR-Cas12a results in more than 70% suppression of −1 PRF in vitro and about 50% suppression in mammalian cells. Our results show the expanded function of the CRISPR-Cas12 system in modulating −1 PRF efficiency through stalling ribosomes and deforming frameshifting stimulatory signals, which could serve as a new strategy for future coronavirus pandemics.
    日期: 2023-12-15
    關聯: iScience. 2023 Dec 15;26(12):Article number 108492.
    Link to: http://dx.doi.org/10.1016/j.isci.2023.108492
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2589-0042&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001133635300001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85178384305
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