Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed −1 ribosomal frameshifting

• DOI: 10.1016/j.celrep.2023.112987
• Publication Date: 2023-08-14T10:52:36Z
• Authors: Lian-Huan Wei; Yu Sun; Junjie U. Guo
• Keywords: Translational frameshift; Eukaryotic translation; Initiation factor

Many positive-strand RNA viruses, including all known coronaviruses, employ programmed -1 ribosomal frameshifting (-1 PRF) to regulate the translation of polycistronic viral RNAs. However, only a few host factors have been shown PRF. Through genome-wide CRISPR-Cas9 knockout screen, we identified that either suppress or enhance severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Among them, eukaryotic initiation factor 2A (eIF2A) specifically and directly enhances PRF independent changes in initiation. Consistent with crucial role efficient transcriptase/replicase expression, loss eIF2A reduces SARS-CoV-2 replication cells. Furthermore, transcriptome-wide analysis shows preferentially binds CG-rich motifs, region within 18S near contacts between frameshift-stimulatory element (FSE) ribosome. Thus, our results indicate for modulating specific RNAs its during