PMID- 33836091
OWN - NLM
STAT- MEDLINE
DCOM- 20210616
LR  - 20231111
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 49
IP  - 8
DP  - 2021 May 7
TI  - A purine loop and the primer binding site are critical for the selective 
      encapsidation of mouse mammary tumor virus genomic RNA by Pr77Gag.
PG  - 4668-4688
LID - 10.1093/nar/gkab223 [doi]
AB  - Retroviral RNA genome (gRNA) harbors cis-acting sequences that facilitate its 
      specific packaging from a pool of other viral and cellular RNAs by binding with 
      high-affinity to the viral Gag protein during virus assembly. However, the 
      molecular intricacies involved during selective gRNA packaging are poorly 
      understood. Binding and footprinting assays on mouse mammary tumor virus (MMTV) 
      gRNA with purified Pr77Gag along with in cell gRNA packaging study identified two 
      Pr77Gag binding sites constituting critical, non-redundant packaging signals. 
      These included: a purine loop in a bifurcated stem-loop containing the gRNA 
      dimerization initiation site, and the primer binding site (PBS). Despite these 
      sites being present on both unspliced and spliced RNAs, Pr77Gag specifically 
      bound to unspliced RNA, since only that could adopt the native bifurcated 
      stem-loop structure containing looped purines. These results map minimum 
      structural elements required to initiate MMTV gRNA packaging, distinguishing 
      features that are conserved amongst divergent retroviruses from those perhaps 
      unique to MMTV. Unlike purine-rich motifs frequently associated with packaging 
      signals, direct involvement of PBS in gRNA packaging has not been documented in 
      retroviruses. These results enhance our understanding of retroviral gRNA 
      packaging/assembly, making it not only a target for novel therapeutic 
      interventions, but also development of safer gene therapy vectors.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Chameettachal, Akhil
AU  - Chameettachal A
AUID- ORCID: 0000-0003-1944-6726
AD  - Department of Microbiology & Immunology, College of Medicine and Health Sciences 
      (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
FAU - Vivet-Boudou, Valerie
AU  - Vivet-Boudou V
AD  - Universite de Strasbourg, CNRS, Architecture et Reactivite de l'ARN, UPR 9002, 
      Strasbourg, France.
FAU - Pitchai, Fathima Nuzra Nagoor
AU  - Pitchai FNN
AD  - Department of Microbiology & Immunology, College of Medicine and Health Sciences 
      (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
FAU - Pillai, Vineeta N
AU  - Pillai VN
AD  - Department of Microbiology & Immunology, College of Medicine and Health Sciences 
      (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
FAU - Ali, Lizna Mohamed
AU  - Ali LM
AD  - Department of Microbiology & Immunology, College of Medicine and Health Sciences 
      (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
FAU - Krishnan, Anjana
AU  - Krishnan A
AD  - Department of Microbiology & Immunology, College of Medicine and Health Sciences 
      (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
FAU - Bernacchi, Serena
AU  - Bernacchi S
AUID- ORCID: 0000-0003-2824-8326
AD  - Universite de Strasbourg, CNRS, Architecture et Reactivite de l'ARN, UPR 9002, 
      Strasbourg, France.
FAU - Mustafa, Farah
AU  - Mustafa F
AUID- ORCID: 0000-0002-1081-3756
AD  - Department of Biochemistry, College of Medicine and Health Sciences (CMHS), 
      United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
AD  - Zayed Center for Health Sciences, United Arab Emirates University, United Arab 
      Emirates.
FAU - Marquet, Roland
AU  - Marquet R
AUID- ORCID: 0000-0002-4209-3976
AD  - Universite de Strasbourg, CNRS, Architecture et Reactivite de l'ARN, UPR 9002, 
      Strasbourg, France.
FAU - Rizvi, Tahir A
AU  - Rizvi TA
AUID- ORCID: 0000-0002-2572-1678
AD  - Department of Microbiology & Immunology, College of Medicine and Health Sciences 
      (CMHS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
AD  - Zayed Center for Health Sciences, United Arab Emirates University, United Arab 
      Emirates.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (DNA Primers)
RN  - 0 (Gene Products, gag)
RN  - 0 (Purines)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Animals
MH  - Binding Sites/genetics
MH  - DNA Primers
MH  - Dynamic Light Scattering
MH  - Gene Products, gag/genetics/*metabolism
MH  - Genome, Viral
MH  - Mammary Tumor Virus, Mouse/genetics/*metabolism
MH  - Mice
MH  - Nucleic Acid Conformation
MH  - Purines
MH  - *RNA Splicing
MH  - RNA, Viral/genetics/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Virus Assembly/*genetics
PMC - PMC8096270
EDAT- 2021/04/10 06:00
MHDA- 2021/06/17 06:00
PMCR- 2021/04/09
CRDT- 2021/04/09 17:19
PHST- 2021/03/24 00:00 [accepted]
PHST- 2021/03/15 00:00 [revised]
PHST- 2020/06/11 00:00 [received]
PHST- 2021/04/10 06:00 [pubmed]
PHST- 2021/06/17 06:00 [medline]
PHST- 2021/04/09 17:19 [entrez]
PHST- 2021/04/09 00:00 [pmc-release]
AID - 6219124 [pii]
AID - gkab223 [pii]
AID - 10.1093/nar/gkab223 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2021 May 7;49(8):4668-4688. doi: 10.1093/nar/gkab223.