Co-translational Localization of an LTR-Retrotransposon RNA to the Endoplasmic Reticulum Nucleates Virus-Like Particle Assembly Sites


Retrotransposons are mobile elements that have invaded the genomes of organisms from bacteria to humans. Facilitated by host co-factors, retrotransposon proteins copy their RNA genomes into DNA that integrates into the host genome, causing mutations and genome instability. The yeast Ty1 element belongs to a family of retrotransposons that are related to infectious retroviruses. Ty1 RNA and its coat protein, Gag, assemble into virus-like particles, wherein the RNA is copied into DNA. It was not previously known how Ty1 RNA and Gag are concentrated in a specific cellular location to initiate the assembly of virus-like particles. In this study, we show that Ty1 RNA is brought to the presumptive assembly site during translation by the protein chaperone, signal recognition particle. As Ty1 RNA is translated, the nascent Gag polypeptide enters the lumen of the endoplasmic reticulum, where Gag adopts a stable conformation before returning to the cytoplasm to bind to translating Ty1 RNA. An interaction between Gag molecules bound to translating Ty1 RNA results in the nucleation of the virus-like particle assembly site. Our findings identify new host co-factors in retrotransposon mobility and suggest potential approaches to controlling retrotransposon-associated genome instability in aging and cancer.


Vyšlo v časopise: Co-translational Localization of an LTR-Retrotransposon RNA to the Endoplasmic Reticulum Nucleates Virus-Like Particle Assembly Sites. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004219
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004219

Souhrn

Retrotransposons are mobile elements that have invaded the genomes of organisms from bacteria to humans. Facilitated by host co-factors, retrotransposon proteins copy their RNA genomes into DNA that integrates into the host genome, causing mutations and genome instability. The yeast Ty1 element belongs to a family of retrotransposons that are related to infectious retroviruses. Ty1 RNA and its coat protein, Gag, assemble into virus-like particles, wherein the RNA is copied into DNA. It was not previously known how Ty1 RNA and Gag are concentrated in a specific cellular location to initiate the assembly of virus-like particles. In this study, we show that Ty1 RNA is brought to the presumptive assembly site during translation by the protein chaperone, signal recognition particle. As Ty1 RNA is translated, the nascent Gag polypeptide enters the lumen of the endoplasmic reticulum, where Gag adopts a stable conformation before returning to the cytoplasm to bind to translating Ty1 RNA. An interaction between Gag molecules bound to translating Ty1 RNA results in the nucleation of the virus-like particle assembly site. Our findings identify new host co-factors in retrotransposon mobility and suggest potential approaches to controlling retrotransposon-associated genome instability in aging and cancer.


Zdroje

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