Structural Mimicry Drives HIV-1 Rev-Mediated HERV-K Expression
Abstract
Expression of the Human Endogenous Retrovirus Type K (HERV-K), the youngest and most active HERV, has been associated with various cancers and neurodegenerative diseases. As in all retroviruses, a fraction of HERV-K transcripts is exported from the nucleus in unspliced or incompletely spliced forms to serve as templates for translation of viral proteins. In a fraction of HERV-K loci (Type 2 proviruses), nuclear export of the unspliced HERV-K mRNA appears to be mediated by a cis-acting signal on the mRNA, the RcRE, and the protein Rec—these are analogous to the RRE-Rev system in HIV-1. Interestingly, the HIV-1 Rev protein is able to mediate the nuclear export of the HERV-K RcRE, contributing to elevated HERV-K expression in HIV-infected patients. We aimed to understand the structural basis for HIV Rev-HERV-K RcRE recognition. We examined the conformation of the RcRE RNA in solution using small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM). We found that the 433-nt long RcRE can assume folded or extended conformations as observed by AFM. SAXS analysis of a truncated RcRE variant revealed an “A”-shaped topological structure similar to the one previously reported for the HIV-1 RRE. The effect of the overall topology was examined using several deletionmore »
- Authors:
-
- United States Naval Academy, Annapolis, MD (United States)
- SAXS Core Facility of the National Cancer Institute, Frederick, MD (United States)
- National Inst. of Health, Frederick, MD (United States)
- United States Naval Academy, Annapolis, MD (United States); Stanford School of Medicine, Stanford, CA (United States)
- Publication Date:
- Research Org.:
- United States Naval Academy, Annapolis, MD (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Institutes of Health (NIH)
- OSTI Identifier:
- 1713061
- Alternate Identifier(s):
- OSTI ID: 1775965
- Grant/Contract Number:
- AC02-06CH11357; HHSN26120080001E
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Molecular Biology
- Additional Journal Information:
- Journal Volume: 432; Journal Issue: 24; Related Information: Ina P. O'Carroll, Lixin Fan, Tomas Kroupa, Erin K. McShane, Christophe Theodore, Elizabeth A. Yates, Benjamin Kondrup, Jienyu Ding, Tyler S. Martin, Alan Rein, Yun-Xing Wang,Structural mimicry drives HIV-1 Rev-mediated HERV-K expression,Journal of Molecular Biology, 2020. https://doi.org/10.1016/j.jmb.2020.11.010.; Journal ID: ISSN 0022-2836
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; HERV-K; RcRE; small-angle X-ray scattering; atomic force microscopy; HIV-1 Rev
Citation Formats
O'Carroll, Ina P., Fan, Lixin, Kroupa, Tomáš, McShane, Erin K., Theodore, Christophe, Yates, Elizabeth A., Kondrup, Benjamin, Ding, Jienyu, Martin, Tyler S., Rein, Alan, and Wang, Yun-Xing. Structural Mimicry Drives HIV-1 Rev-Mediated HERV-K Expression. United States: N. p., 2020.
Web. doi:10.1016/j.jmb.2020.11.010.
O'Carroll, Ina P., Fan, Lixin, Kroupa, Tomáš, McShane, Erin K., Theodore, Christophe, Yates, Elizabeth A., Kondrup, Benjamin, Ding, Jienyu, Martin, Tyler S., Rein, Alan, & Wang, Yun-Xing. Structural Mimicry Drives HIV-1 Rev-Mediated HERV-K Expression. United States. https://doi.org/10.1016/j.jmb.2020.11.010
O'Carroll, Ina P., Fan, Lixin, Kroupa, Tomáš, McShane, Erin K., Theodore, Christophe, Yates, Elizabeth A., Kondrup, Benjamin, Ding, Jienyu, Martin, Tyler S., Rein, Alan, and Wang, Yun-Xing. Sat .
"Structural Mimicry Drives HIV-1 Rev-Mediated HERV-K Expression". United States. https://doi.org/10.1016/j.jmb.2020.11.010. https://www.osti.gov/servlets/purl/1713061.
@article{osti_1713061,
title = {Structural Mimicry Drives HIV-1 Rev-Mediated HERV-K Expression},
author = {O'Carroll, Ina P. and Fan, Lixin and Kroupa, Tomáš and McShane, Erin K. and Theodore, Christophe and Yates, Elizabeth A. and Kondrup, Benjamin and Ding, Jienyu and Martin, Tyler S. and Rein, Alan and Wang, Yun-Xing},
abstractNote = {Expression of the Human Endogenous Retrovirus Type K (HERV-K), the youngest and most active HERV, has been associated with various cancers and neurodegenerative diseases. As in all retroviruses, a fraction of HERV-K transcripts is exported from the nucleus in unspliced or incompletely spliced forms to serve as templates for translation of viral proteins. In a fraction of HERV-K loci (Type 2 proviruses), nuclear export of the unspliced HERV-K mRNA appears to be mediated by a cis-acting signal on the mRNA, the RcRE, and the protein Rec—these are analogous to the RRE-Rev system in HIV-1. Interestingly, the HIV-1 Rev protein is able to mediate the nuclear export of the HERV-K RcRE, contributing to elevated HERV-K expression in HIV-infected patients. We aimed to understand the structural basis for HIV Rev-HERV-K RcRE recognition. We examined the conformation of the RcRE RNA in solution using small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM). We found that the 433-nt long RcRE can assume folded or extended conformations as observed by AFM. SAXS analysis of a truncated RcRE variant revealed an “A”-shaped topological structure similar to the one previously reported for the HIV-1 RRE. The effect of the overall topology was examined using several deletion variants. SAXS and biochemical analyses demonstrated that the “A” shape is necessary for efficient Rev-RcRE complex formation in vitro and nuclear export activity in cell culture. Here, the findings provide insight into the mechanism of HERV-K expression and a structural explanation for HIV-1 Rev-mediated expression of HERV-K in HIV-infected patients.},
doi = {10.1016/j.jmb.2020.11.010},
journal = {Journal of Molecular Biology},
number = 24,
volume = 432,
place = {United States},
year = {Sat Nov 14 00:00:00 EST 2020},
month = {Sat Nov 14 00:00:00 EST 2020}
}
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