Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag

Tiffiny Rye-McCurdy, Erik D. Olson, Shuohui Liu, Christiana Binkley, Joshua Paolo Reyes, Brian R. Thompson, John M. Flanagan, Leslie J. Parent, Karin Musier-Forsyth

Research output: Contribution to journalArticle

  • 2 Citations

Abstract

Retroviruses specifically package full-length, dimeric genomic RNA (gRNA) even in the presence of a vast excess of cellular RNA. The “psi” (ψ) element within the 5ʹ-untranslated region (5ʹUTR) of gRNA is critical for packaging through interaction with the nucleocapsid (NC) domain of Gag. However, in vitro Gag binding affinity for ψ versus non-ψ RNAs is not significantly different. Previous salt-titration binding assays revealed that human immunodeficiency virus type 1 (HIV-1) Gag bound to ψ RNA with high specificity and relatively few charge interactions, whereas binding to non-ψ RNA was less specific and involved more electrostatic interactions. The NC domain was critical for specific ψ binding, but surprisingly, a Gag mutant lacking the matrix (MA) domain was less effective at discriminating ψ from non-ψ RNA. We now find that Rous sarcoma virus (RSV) Gag also effectively discriminates RSV ψ from non-ψ RNA in a MA-dependent manner. Interestingly, Gag chimeras, wherein the HIV-1 and RSV MA domains were swapped, maintained high binding specificity to cognate ψ RNAs. Using ψ RNA mutant constructs, determinants responsible for promoting high Gag binding specificity were identified in both systems. Taken together, these studies reveal the functional equivalence of HIV-1 and RSV MA domains in facilitating ψ RNA selectivity by Gag, as well as ψ elements that promote this selectivity.

LanguageEnglish (US)
Article number256
JournalViruses
Volume8
Issue number9
DOIs
StatePublished - Sep 20 2016

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RNA
Rous sarcoma virus
HIV-1
Nucleocapsid
5' Untranslated Regions
Product Packaging
Retroviridae
Static Electricity
Salts

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

Cite this

Rye-McCurdy, T., Olson, E. D., Liu, S., Binkley, C., Reyes, J. P., Thompson, B. R., ... Musier-Forsyth, K. (2016). Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag. Viruses, 8(9), [256]. DOI: 10.3390/v8090256
Rye-McCurdy, Tiffiny ; Olson, Erik D. ; Liu, Shuohui ; Binkley, Christiana ; Reyes, Joshua Paolo ; Thompson, Brian R. ; Flanagan, John M. ; Parent, Leslie J. ; Musier-Forsyth, Karin. / Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag. In: Viruses. 2016 ; Vol. 8, No. 9.
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Rye-McCurdy, T, Olson, ED, Liu, S, Binkley, C, Reyes, JP, Thompson, BR, Flanagan, JM, Parent, LJ & Musier-Forsyth, K 2016, 'Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag' Viruses, vol 8, no. 9, 256. DOI: 10.3390/v8090256

Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag. / Rye-McCurdy, Tiffiny; Olson, Erik D.; Liu, Shuohui; Binkley, Christiana; Reyes, Joshua Paolo; Thompson, Brian R.; Flanagan, John M.; Parent, Leslie J.; Musier-Forsyth, Karin.

In: Viruses, Vol. 8, No. 9, 256, 20.09.2016.

Research output: Contribution to journalArticle

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Rye-McCurdy T, Olson ED, Liu S, Binkley C, Reyes JP, Thompson BR et al. Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag. Viruses. 2016 Sep 20;8(9). 256. Available from, DOI: 10.3390/v8090256