2. Academic Validation
  3. Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting

Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting

  • Cell. 2019 Jan 24;176(3):625-635.e14. doi: 10.1016/j.cell.2018.12.030.
Xinlu Wang 1,  Yifang Xuan 1,  Yuling Han 2,  Xiang Ding 3,  Kai Ye 1,  Fuquan Yang 3,  Pu Gao 1,  Stephen P Goff 4,  Guangxia Gao 5
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Infection and Immunity, CAS Centre for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 2 CAS Key Laboratory of Infection and Immunity, CAS Centre for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 University of Chinese Academy of Sciences, Beijing 100049, China; Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 Departments of Biochemistry and Molecular Biophysics, and of Microbiology and Immunology, and at the Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
  • 5 CAS Key Laboratory of Infection and Immunity, CAS Centre for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: gaogx@moon.ibp.ac.cn.
PMID: 30682371 DOI: 10.1016/j.cell.2018.12.030
Abstract

Programmed -1 ribosomal frameshifting (-1PRF) is a widely used translation recoding mechanism. HIV-1 expresses Gag-Pol protein from the Gag-coding mRNA through -1PRF, and the ratio of Gag to Gag-Pol is strictly maintained for efficient viral replication. Here, we report that the interferon-stimulated gene product C19orf66 (herein named Shiftless) is a host factor that inhibits the -1PRF of HIV-1. Shiftless (SFL) also inhibited the -1PRF of a variety of mRNAs from both viruses and cellular genes. SFL interacted with the -1PRF signal of target mRNA and translating ribosomes and caused premature translation termination at the frameshifting site. Downregulation of translation release factor eRF3 or eRF1 reduced SFL-mediated premature translation termination. We propose that SFL binding to target mRNA and the translating ribosome interferes with the frameshifting process. These findings identify SFL as a broad-spectrum inhibitor of -1PRF and help to further elucidate the mechanisms of -1PRF.

Keywords

Gag-Pol; HIV-1; host antiviral factor; premature translation termination; programmed -1 ribosomal frameshifting; translation recoding.

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