Translation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors.

Autor: Wang F; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Holmes MJ; Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Hong HJ; Department of Biochemistry, University of California Riverside, Riverside, CA, 92521, USA., Thaprawat P; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.; Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Kannan G; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Huynh MH; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Schultz TL; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Licon MH; Whitehead Institute, Cambridge, MA, 02142, USA., Lourido S; Whitehead Institute, Cambridge, MA, 02142, USA.; Biology Department, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA., Dong W; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA.; Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, 48109, USA., Brito Querido J; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA.; Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, 48109, USA., Sullivan WJ Jr; Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., O'Leary SE; Department of Biochemistry, University of California Riverside, Riverside, CA, 92521, USA.; Center for RNA Biology and Medicine, University of California Riverside, Riverside, CA, 92521, USA., Carruthers VB; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. vcarruth@umich.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 23; Vol. 15 (1), pp. 4385. Date of Electronic Publication: 2024 May 23.
DOI: 10.1038/s41467-024-48685-4
Abstrakt: The parasite Toxoplasma gondii persists in its hosts by converting from replicating tachyzoites to latent bradyzoites housed in tissue cysts. The molecular mechanisms that mediate T. gondii differentiation remain poorly understood. Through a mutagenesis screen, we identified translation initiation factor eIF1.2 as a critical factor for T. gondii differentiation. A F97L mutation in eIF1.2 or the genetic ablation of eIF1.2 (∆eif1.2) markedly impeded bradyzoite cyst formation in vitro and in vivo. We demonstrated, at single-molecule level, that the eIF1.2 F97L mutation impacts the scanning process of the ribosome preinitiation complex on a model mRNA. RNA sequencing and ribosome profiling experiments unveiled that ∆eif1.2 parasites are defective in upregulating bradyzoite induction factors BFD1 and BFD2 during stress-induced differentiation. Forced expression of BFD1 or BFD2 significantly restored differentiation in ∆eif1.2 parasites. Together, our findings suggest that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish chronic toxoplasmosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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