Identification of Pr78Gag Binding Sites on the Mason-Pfizer Monkey Virus Genomic RNA Packaging Determinants

Fathima Nuzra Nagoor Pitchai, Akhil Chameettachal, Valérie Vivet-Boudou, Lizna Mohamed Ali, Vineeta N. Pillai, Anjana Krishnan, Serena Bernacchi, Farah Mustafa, Roland Marquet, Tahir A. Rizvi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

How retroviral Gag proteins recognize the packaging signals (Psi) on their genomic RNA (gRNA) is a key question that we addressed here using Mason-Pfizer monkey virus (MPMV) as a model system by combining band-shift assays and footprinting experiments. Our data show that Pr78Gag selects gRNA against spliced viral RNA by simultaneously binding to two single stranded loops on the MPMV Psi RNA: (1) a large purine loop (ssPurines), and (2) a loop which partially overlaps with a mostly base-paired purine repeat (bpPurines) and extends into a GU-rich binding motif. Importantly, this second Gag binding site is located immediately downstream of the major splice donor (mSD) and is thus absent from the spliced viral RNAs. Identifying elements crucial for MPMV gRNA packaging should help in understanding not only the mechanism of virion assembly by retroviruses, but also facilitate construction of safer retroviral vectors for human gene therapy.

Original languageEnglish
Article number166923
JournalJournal of Molecular Biology
Volume433
Issue number10
DOIs
Publication statusPublished - May 14 2021

Keywords

  • Footprinting
  • Gag-RNA interactions
  • Purines
  • Retroviruses
  • hSHAPE

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology

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