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, USA., Armbruster EG; Department of Molecular Biology, University of California San Diego, La Jolla, CA, USA., Lee J; Department of Molecular Biology, University of California San Diego, La Jolla, CA, USA., Zhang S; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Yee BA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Gu Y; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Deep A; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Naritomi JT; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Liang Q; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Aigner S; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Adler BA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA.; Innovative Genomics Institute, University of California, Berkeley, CA, USA., Cress BF; Innovative Genomics Institute, University of California, Berkeley, CA, USA., Doudna JA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA.; Innovative Genomics Institute, University of California, Berkeley, CA, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.; Department of Chemistry, University of California, Berkeley, CA, USA.; Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., Chaikeeratisak V; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand., Cleveland DW; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.; Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, 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, USA., Yeo GW; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 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, USA., Corbett KD; Department of Molecular Biology, University of California San Diego, La Jolla, CA, USA.; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.; Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 22. Date of Electronic Publication: 2023 Sep 22.
DOI:	10.1101/2023.09.22.559000
Abstrakt:	Large-genome bacteriophages (jumbo phages) of the Chimalliviridae family assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and 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 halts infections at an early stage. Taken together, our data suggest that the conserved ChmC protein acts as a chaperone for phage mRNAs, potentially stabilizing these mRNAs and driving their translocation through the nuclear shell to promote translation and infection progression. Competing Interests: J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Vertex, Caribou Biosciences, Intellia Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Algen Biotechnologies, Felix Biosciences, The Column Group and Inari. J.A.D. is Chief Science Advisor to Sixth Street, a Director at Johnson & Johnson, Altos and Tempus, and has research projects sponsored by Apple Tree Partners and Roche. G.W.Y. is an SAB member of Jumpcode Genomics and a co-founder, member of the Board of Directors, on the SAB, equity holder, and paid consultant for Locanabio and Eclipse BioInnovations. G.W.Y. is a distinguished visiting professor at the National University of Singapore. G.W.Y.’s interests have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. The Regents of the University of California have filed a provisional patent application for CRISPR technologies on which B.A.A., B.F.C., E.J.A., J.L., J.A.P., are J.A.D. are inventors.
Databáze:	MEDLINE
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