A phage nucleus-associated RNA-binding protein is required for jumbo phage infection.
Autor: | Enustun E; Department of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA., Armbruster EG; Department of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA., Lee J; Department of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA., Zhang S; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Yee BA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Malukhina K; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Gu Y; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Deep A; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Naritomi JT; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Liang Q; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Aigner S; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Adler BA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA.; Innovative Genomics Institute, University of California, Berkeley, CA 94720, USA., Cress BF; Innovative Genomics Institute, University of California, Berkeley, CA 94720, USA., Doudna JA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA.; Innovative Genomics Institute, University of California, Berkeley, CA 94720, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.; Department of Chemistry, University of California, Berkeley, CA 94720, USA.; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA., Chaikeeratisak V; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand., Cleveland DW; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.; Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA., Ghassemian M; Biomolecular and Proteomics Mass Spectrometry Facility, University of California San Diego, La Jolla, CA 92093, USA., Bintu B; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Yeo GW; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.; Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA., Pogliano J; Department of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA., Corbett KD; Department of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA.; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.; Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA. |
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Jazyk: | angličtina |
Zdroj: | Nucleic acids research [Nucleic Acids Res] 2024 May 08; Vol. 52 (8), pp. 4440-4455. |
DOI: | 10.1093/nar/gkae216 |
Abstrakt: | Large-genome bacteriophages (jumbo phages) of the proposed family Chimalliviridae assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and DNA-targeting CRISPR-Cas nucleases. While the nuclear shell provides broad protection against host nucleases, it necessitates transport of mRNA out of the nucleus-like compartment for translation by host ribosomes, and transport of specific proteins into the nucleus-like compartment to support DNA replication and mRNA transcription. Here, we identify a conserved phage nuclear shell-associated protein that we term Chimallin C (ChmC), which adopts a nucleic acid-binding fold, binds RNA with high affinity in vitro, and binds phage mRNAs in infected cells. ChmC also forms phase-separated condensates with RNA in vitro. Targeted knockdown of ChmC using mRNA-targeting dCas13d results in accumulation of phage-encoded mRNAs in the phage nucleus, reduces phage protein production, and compromises virion assembly. Taken together, our data show that the conserved ChmC protein plays crucial roles in the viral life cycle, potentially by facilitating phage mRNA translocation through the nuclear shell to promote protein production and virion development. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.) |
Databáze: | MEDLINE |
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