tetano
Editor, Senior Moderator
Cell Rep
. 2023 Aug 14;42(8):112987.
doi: 10.1016/j.celrep.2023.112987. Online ahead of print. Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting
Lian-Huan Wei[SUP] 1 [/SUP], Yu Sun[SUP] 1 [/SUP], Junjie U Guo[SUP] 2 [/SUP]
Affiliations
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 to regulate -1 PRF. Through a genome-wide CRISPR-Cas9 knockout screen, we have identified host factors that either suppress or enhance severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -1 PRF. Among them, eukaryotic translation initiation factor 2A (eIF2A) specifically and directly enhances -1 PRF independent of changes in initiation. Consistent with the crucial role of efficient -1 PRF in transcriptase/replicase expression, loss of eIF2A reduces SARS-CoV-2 replication in cells. Furthermore, transcriptome-wide analysis shows that eIF2A preferentially binds CG-rich RNA motifs, including a region within 18S ribosomal RNA near the contacts between the SARS-CoV-2 frameshift-stimulatory element (FSE) and the ribosome. Thus, our results indicate a role for eIF2A in modulating the translation of specific RNAs independent of its role during initiation.
Keywords: CP: Microbiology; CRISPR screen; SARS-CoV-2; eIF2A; programmed −1 ribosomal frameshifting; translation.
. 2023 Aug 14;42(8):112987.
doi: 10.1016/j.celrep.2023.112987. Online ahead of print. Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting
Lian-Huan Wei[SUP] 1 [/SUP], Yu Sun[SUP] 1 [/SUP], Junjie U Guo[SUP] 2 [/SUP]
Affiliations
- PMID: 37581984
- DOI: 10.1016/j.celrep.2023.112987
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 to regulate -1 PRF. Through a genome-wide CRISPR-Cas9 knockout screen, we have identified host factors that either suppress or enhance severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -1 PRF. Among them, eukaryotic translation initiation factor 2A (eIF2A) specifically and directly enhances -1 PRF independent of changes in initiation. Consistent with the crucial role of efficient -1 PRF in transcriptase/replicase expression, loss of eIF2A reduces SARS-CoV-2 replication in cells. Furthermore, transcriptome-wide analysis shows that eIF2A preferentially binds CG-rich RNA motifs, including a region within 18S ribosomal RNA near the contacts between the SARS-CoV-2 frameshift-stimulatory element (FSE) and the ribosome. Thus, our results indicate a role for eIF2A in modulating the translation of specific RNAs independent of its role during initiation.
Keywords: CP: Microbiology; CRISPR screen; SARS-CoV-2; eIF2A; programmed −1 ribosomal frameshifting; translation.