MMTV RNA packaging requires an extended long-range interaction for productive Gag binding to packaging signals.

Autor: Prabhu SG; Department of Microbiology & Immunology, College of Medicine and Health Sciences (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates., Pillai VN; Department of Microbiology & Immunology, College of Medicine and Health Sciences (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates., Ali LM; Department of Microbiology & Immunology, College of Medicine and Health Sciences (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates., Vivet-Boudou V; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, Strasbourg, France., Chameettachal A; Department of Microbiology & Immunology, College of Medicine and Health Sciences (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates., Bernacchi S; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, Strasbourg, France., Mustafa F; Department of Biochemistry & Molecular Biology, College of Medicine and Health Sciences (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.; Zayed bin Sultan Center for Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.; ASPIRE Research Institute in Precision Medicine, Abu Dhabi, United Arab Emirates., Marquet R; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, Strasbourg, France., Rizvi TA; Department of Microbiology & Immunology, College of Medicine and Health Sciences (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.; Zayed bin Sultan Center for Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.; ASPIRE Research Institute in Precision Medicine, Abu Dhabi, United Arab Emirates.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Oct 03; Vol. 22 (10), pp. e3002827. Date of Electronic Publication: 2024 Oct 03 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002827
Abstrakt: The packaging of genomic RNA (gRNA) into retroviral particles relies on the specific recognition by the Gag precursor of packaging signals (Psi), which maintain a complex secondary structure through long-range interactions (LRIs). However, it remains unclear whether the binding of Gag to Psi alone is enough to promote RNA packaging and what role LRIs play in this process. Using mouse mammary tumor virus (MMTV), we investigated the effects of mutations in 4 proposed LRIs on gRNA structure and function. Our findings revealed the presence of an unsuspected extended LRI, and hSHAPE revealed that maintaining a wild-type-like Psi structure is crucial for efficient packaging. Surprisingly, filter-binding assays demonstrated that most mutants, regardless of their packaging capability, exhibited significant binding to Pr77Gag, suggesting that Gag binding to Psi is insufficient for efficient packaging. Footprinting experiments indicated that efficient RNA packaging is promoted when Pr77Gag binds to 2 specific sites within Psi, whereas binding elsewhere in Psi does not lead to efficient packaging. Taken together, our results suggest that the 3D structure of the Psi/Pr77Gag complex regulates the assembly of viral particles around gRNA, enabling effective discrimination against other viral and cellular RNAs that may also bind Gag efficiently.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Prabhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE