Caenorhabditis elegans SynMuv B gene activity is down-regulated during a viral infection to enhance RNA interference.

Autor:	Seetharaman A; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02114 USA., Galagali H; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02114 USA., Linarte E; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.; University of Massachusetts, Lowell, Massachusetts, USA., Liu MHX; Harvard Medical School, Boston, MA, USA, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Cohen JD; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02114 USA.; Department of Microbiology, Harvard Medical School, Massachusetts, USA., Chetal K; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02114 USA., Sadreyev R; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Tate AJ; Department of Biology, Colorado State University, Fort Collins, CO, USA., Montgomery TA; Department of Biology, Colorado State University, Fort Collins, CO, USA., Ruvkun G; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02114 USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 16. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1101/2024.07.12.603258
Abstrakt:	Small RNA pathways regulate eukaryotic antiviral defense. Many of the Caenorhabditis elegans mutations that were identified based on their enhanced RNAi, the synMuv B genes, also emerged from unrelated genetic screens for increased growth factor signaling. The dozen synMuv B genes encode homologues of the mammalian dREAM complex found in nearly all animals and plants, which includes the lin-35 /retinoblastoma oncogene. We show that a set of highly induced mRNAs in synMuv B mutants is congruent with mRNAs induced by Orsay RNA virus infection of C . elegans . In wild type animals, a combination of a synMuv A mutation and a synMuv B mutation are required for the Muv phenotype of increased growth factor signaling. But we show that Orsay virus infection of a single synMuv A mutant can induce a Muv phenotype, unlike the uninfected single synMuv A mutant. This suggests that decreased synMuv B activity, which activates the antiviral RNAi pathway, is a defense response to viral infection. Small RNA deep sequencing analysis of various dREAM complex mutants uncovers distinct siRNA profiles indicative of such an siRNA response. We conclude that the synMuv B mutants maintain an antiviral readiness state even in the absence of actual infection. The enhanced RNAi and conservation of the dREAM complex mutants suggests new therapeutic avenues to boost antiviral defenses.
Databáze:	MEDLINE
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