Journal article
The Ty1 Retrotransposon Restriction Factor p22 Targets Gag
PLoS genetics, Vol.11(10), pp.e1005571-e1005571
10/01/2015
DOI: 10.1371/journal.pgen.1005571
PMCID: PMC4599808
PMID: 26451601
Abstract
A novel form of copy number control (CNC) helps maintain a low number of Ty1 retrovirus-like transposons in the Saccharomyces genome. Ty1 produces an alternative transcript that encodes p22, a trans-dominant negative inhibitor of Ty1 retrotransposition whose sequence is identical to the C-terminal half of Gag. The level of p22 increases with copy number and inhibits normal Ty1 virus-like particle (VLP) assembly and maturation through interactions with full length Gag. A forward genetic screen for CNC-resistant (CNCR) mutations in Ty1 identified missense mutations in GAG that restore retrotransposition in the presence of p22. Some of these mutations map within a predicted UBN2 domain found throughout the Ty1/copia family of long terminal repeat retrotransposons, and others cluster within a central region of Gag that is referred to as the CNCR domain. We generated multiple alignments of yeast Ty1-like Gag proteins and found that some Gag proteins, including those of the related Ty2 elements, contain non-Ty1 residues at multiple CNCR sites. Interestingly, the Ty2-917 element is resistant to p22 and does not undergo a Ty1-like form of CNC. Substitutions conferring CNCR map within predicted helices in Ty1 Gag that overlap with conserved sequence in Ty1/copia, suggesting that p22 disturbs a central function of the capsid during VLP assembly. When hydrophobic residues within predicted helices in Gag are mutated, Gag level remains unaffected in most cases yet VLP assembly and maturation is abnormal. Gag CNCR mutations do not alter binding to p22 as determined by co-immunoprecipitation analyses, but instead, exclude p22 from Ty1 VLPs. These findings suggest that the CNCR alleles enhance retrotransposition in the presence of p22 by allowing productive Gag-Gag interactions during VLP assembly. Our work also expands the strategies used by retroviruses for developing resistance to Gag-like restriction factors to now include retrotransposons.
Details
- Title: Subtitle
- The Ty1 Retrotransposon Restriction Factor p22 Targets Gag
- Creators
- Jessica M. Tucker - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America.Morgan E. Larango - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America.Lucas P. Wachsmuth - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America.Natarajan Kannan - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America.David J. Garfinkel - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America.
- Resource Type
- Journal article
- Publication Details
- PLoS genetics, Vol.11(10), pp.e1005571-e1005571
- DOI
- 10.1371/journal.pgen.1005571
- PMID
- 26451601
- PMCID
- PMC4599808
- NLM abbreviation
- PLoS Genet
- ISSN
- 1553-7404
- eISSN
- 1553-7404
- Publisher
- Public Library Science
- Number of pages
- 29
- Grant note
- R01GM095622 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) GM095622 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1011RH25213 / National Science Foundation, Graduate Fellowship; National Science Foundation (NSF) MCB-1149106 / National Science Foundation; National Science Foundation (NSF)
- Language
- English
- Date published
- 10/01/2015
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297424202771
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