PMID- 29929424
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 1555-8584 (Electronic)
IS  - 1547-6286 (Print)
IS  - 1547-6286 (Linking)
VI  - 15
IP  - 8
DP  - 2018
TI  - The bifurcated stem loop 4 (SL4) is crucial for efficient packaging of mouse 
      mammary tumor virus (MMTV) genomic RNA.
PG  - 1047-1059
LID - 10.1080/15476286.2018.1486661 [doi]
AB  - Packaging the mouse mammary tumor virus (MMTV) genomic RNA (gRNA) requires the 
      entire 5' untranslated region (UTR) in conjunction with the first 120 nucleotides 
      of the gag gene. This region includes several palindromic (pal) sequence(s) and 
      stable stem loops (SLs). Among these, stem loop 4 (SL4) adopts a bifurcated 
      structure consisting of three stems, two apical loops, and an internal loop. Pal 
      II, located in one of the apical loops, mediates gRNA dimerization, a process 
      intricately linked to packaging. We thus hypothesized that the bifurcated SL4 
      structure could constitute the major gRNA packaging determinant. To test this 
      hypothesis, the two apical loops and the flanking sequences forming the 
      bifurcated SL4 were individually mutated. These mutations all had deleterious 
      effects on gRNA packaging and propagation. Next, single and compensatory mutants 
      were designed to destabilize then recreate the bifurcated SL4 structure. A 
      structure-function analysis using bioinformatics predictions and RNA chemical 
      probing revealed that mutations that led to the loss of the SL4 bifurcated 
      structure abrogated RNA packaging and propagation, while compensatory mutations 
      that recreated the native SL4 structure restored RNA packaging and propagation to 
      wild type levels. Altogether, our results demonstrate that SL4 constitutes the 
      principal packaging determinant of MMTV gRNA. Our findings further suggest that 
      SL4 acts as a structural switch that can not only differentiate between RNA for 
      translation versus packaging/dimerization, but its location also allows 
      differentiation between spliced and unspliced RNAs during gRNA encapsidation.
FAU - Mustafa, Farah
AU  - Mustafa F
AD  - a Department of Biochemistry , College of Medicine and Health Sciences, United 
      Arab Emirates University , Al Ain , UAE.
FAU - Vivet-Boudou, Valerie
AU  - Vivet-Boudou V
AUID- ORCID: 0000-0001-8702-1047
AD  - b Universite de Strasbourg , CNRS, Architecture et Reactivite de l'ARN , 
      Strasbourg , France.
FAU - Jabeen, Ayesha
AU  - Jabeen A
AD  - c Department of Microbiology & Immunology , College of Medicine and Health 
      Sciences, United Arab Emirates University , Al Ain , UAE.
FAU - Ali, Lizna M
AU  - Ali LM
AD  - c Department of Microbiology & Immunology , College of Medicine and Health 
      Sciences, United Arab Emirates University , Al Ain , UAE.
FAU - Kalloush, Rawan M
AU  - Kalloush RM
AD  - c Department of Microbiology & Immunology , College of Medicine and Health 
      Sciences, United Arab Emirates University , Al Ain , UAE.
FAU - Marquet, Roland
AU  - Marquet R
AD  - b Universite de Strasbourg , CNRS, Architecture et Reactivite de l'ARN , 
      Strasbourg , France.
FAU - Rizvi, Tahir A
AU  - Rizvi TA
AD  - c Department of Microbiology & Immunology , College of Medicine and Health 
      Sciences, United Arab Emirates University , Al Ain , UAE.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180705
PL  - United States
TA  - RNA Biol
JT  - RNA biology
JID - 101235328
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Animals
MH  - *Dimerization
MH  - Genomics
MH  - Mammary Tumor Virus, Mouse/chemistry/genetics/*metabolism
MH  - Mice
MH  - Nucleic Acid Conformation
MH  - *Protein Biosynthesis
MH  - RNA, Viral/*chemistry/genetics/*metabolism
MH  - *Virus Assembly
PMC - PMC6161677
OTO - NOTNLM
OT  - Mouse mammary tumor virus
OT  - RNA packaging and dimerization
OT  - RNA secondary structure
OT  - Retroviruses
OT  - palindrome
EDAT- 2018/06/23 06:00
MHDA- 2018/11/27 06:00
PMCR- 2018/07/05
CRDT- 2018/06/23 06:00
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/06/23 06:00 [entrez]
PHST- 2018/07/05 00:00 [pmc-release]
AID - 1486661 [pii]
AID - 10.1080/15476286.2018.1486661 [doi]
PST - ppublish
SO  - RNA Biol. 2018;15(8):1047-1059. doi: 10.1080/15476286.2018.1486661. Epub 2018 Jul 
      5.