Our Technophile
Ayesha J
Past Research Staff
Ayesha J (2002-2010): Ayesha Jabeen served as a Research Assistant in the Rizvi Laboratory from 2009 to 2014. During her five-year tenure, she was recognized for her dedication, meticulous attention to detail, and deep commitment to research quality. Building on her strong background in academic research, Ayesha has since transitioned into the healthcare sector. She is currently based at Sidra Medicine in Qatar, where she continues to apply the same high standards of professionalism and care to her work.
Publications
2020
Ali, L. M.; Pitchai, F. N. N.; Vivet-Boudou, V.; Chameettachal, A.; Jabeen, A.; Pillai, V. N.; Mustafa, F.; Marquet, R.; Rizvi, T. A.
Role of Purine-Rich Regions in Mason-Pfizer Monkey Virus (MPMV) Genomic RNA Packaging and Propagation Journal Article
In: Front Microbiol, vol. 11, pp. 595410, 2020, ISSN: 1664-302X (Print) 1664-302x.
@article{RN36,
title = {Role of Purine-Rich Regions in Mason-Pfizer Monkey Virus (MPMV) Genomic RNA Packaging and Propagation},
author = {L. M. Ali and F. N. N. Pitchai and V. Vivet-Boudou and A. Chameettachal and A. Jabeen and V. N. Pillai and F. Mustafa and R. Marquet and T. A. Rizvi},
doi = {10.3389/fmicb.2020.595410},
issn = {1664-302X (Print) 1664-302x},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Front Microbiol},
volume = {11},
pages = {595410},
abstract = {A distinguishing feature of the Mason-Pfizer monkey virus (MPMV) packaging signal RNA secondary structure is a single-stranded purine-rich sequence (ssPurines) in close vicinity to a palindromic stem loop (Pal SL) that functions as MPMV dimerization initiation site (DIS). However, unlike other retroviruses, MPMV contains a partially base-paired repeat sequence of ssPurines (bpPurines) in the adjacent region. Both purine-rich sequences have earlier been proposed to act as potentially redundant Gag binding sites to initiate the process of MPMV genomic RNA (gRNA) packaging. The objective of this study was to investigate the biological significance of ssPurines and bpPurines in MPMV gRNA packaging by systematic mutational and biochemical probing analyses. Deletion of either ssPurines or bpPurines individually had no significant effect on MPMV gRNA packaging, but it was severely compromised when both sequences were deleted simultaneously. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) analysis of the mutant RNAs revealed only mild effects on structure by deletion of either ssPurines or bpPurines, while the structure was dramatically affected by the two simultaneous deletions. This suggests that ssPurines and bpPurines play a redundant role in MPMV gRNA packaging, probably as Gag binding sites to facilitate gRNA capture and encapsidation. Interestingly, the deletion of bpPurines revealed an additional severe defect on RNA propagation that was independent of the presence or absence of ssPurines or the gRNA structure of the region. These findings further suggest that the bpPurines play an additional role in the early steps of MPMV replication cycle that is yet to be identified.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A distinguishing feature of the Mason-Pfizer monkey virus (MPMV) packaging signal RNA secondary structure is a single-stranded purine-rich sequence (ssPurines) in close vicinity to a palindromic stem loop (Pal SL) that functions as MPMV dimerization initiation site (DIS). However, unlike other retroviruses, MPMV contains a partially base-paired repeat sequence of ssPurines (bpPurines) in the adjacent region. Both purine-rich sequences have earlier been proposed to act as potentially redundant Gag binding sites to initiate the process of MPMV genomic RNA (gRNA) packaging. The objective of this study was to investigate the biological significance of ssPurines and bpPurines in MPMV gRNA packaging by systematic mutational and biochemical probing analyses. Deletion of either ssPurines or bpPurines individually had no significant effect on MPMV gRNA packaging, but it was severely compromised when both sequences were deleted simultaneously. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) analysis of the mutant RNAs revealed only mild effects on structure by deletion of either ssPurines or bpPurines, while the structure was dramatically affected by the two simultaneous deletions. This suggests that ssPurines and bpPurines play a redundant role in MPMV gRNA packaging, probably as Gag binding sites to facilitate gRNA capture and encapsidation. Interestingly, the deletion of bpPurines revealed an additional severe defect on RNA propagation that was independent of the presence or absence of ssPurines or the gRNA structure of the region. These findings further suggest that the bpPurines play an additional role in the early steps of MPMV replication cycle that is yet to be identified.
2018
Mustafa, F.; Vivet-Boudou, V.; Jabeen, A.; Ali, L. M.; Kalloush, R. M.; Marquet, R.; Rizvi, T. A.
The bifurcated stem loop 4 (SL4) is crucial for efficient packaging of mouse mammary tumor virus (MMTV) genomic RNA Journal Article
In: RNA Biol, vol. 15, no. 8, pp. 1047-1059, 2018, ISSN: 1547-6286 (Print) 1547-6286.
@article{RN90,
title = {The bifurcated stem loop 4 (SL4) is crucial for efficient packaging of mouse mammary tumor virus (MMTV) genomic RNA},
author = {F. Mustafa and V. Vivet-Boudou and A. Jabeen and L. M. Ali and R. M. Kalloush and R. Marquet and T. A. Rizvi},
doi = {10.1080/15476286.2018.1486661},
issn = {1547-6286 (Print) 1547-6286},
year = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
journal = {RNA Biol},
volume = {15},
number = {8},
pages = {1047-1059},
abstract = {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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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.
2014
Aktar, S. J.; Vivet-Boudou, V.; Ali, L. M.; Jabeen, A.; Kalloush, R. M.; Richer, D.; Mustafa, F.; Marquet, R.; Rizvi, T. A.
Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV) Journal Article
In: Retrovirology, vol. 11, pp. 96, 2014, ISSN: 1742-4690.
@article{RN59,
title = {Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV)},
author = {S. J. Aktar and V. Vivet-Boudou and L. M. Ali and A. Jabeen and R. M. Kalloush and D. Richer and F. Mustafa and R. Marquet and T. A. Rizvi},
doi = {10.1186/s12977-014-0096-6},
issn = {1742-4690},
year = {2014},
date = {2014-01-01},
urldate = {2014-01-01},
journal = {Retrovirology},
volume = {11},
pages = {96},
abstract = {BACKGROUND: One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. RESULTS: The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. CONCLUSIONS: Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into the assembling virus particles. The results presented here enhance our understanding of the MMTV gRNA dimerization and packaging processes and the role of structural motifs with respect to RNA-RNA and possibly RNA-protein interactions that might be taking place during MMTV life cycle.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. RESULTS: The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. CONCLUSIONS: Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into the assembling virus particles. The results presented here enhance our understanding of the MMTV gRNA dimerization and packaging processes and the role of structural motifs with respect to RNA-RNA and possibly RNA-protein interactions that might be taking place during MMTV life cycle.
2013
Aktar, S. J.; Jabeen, A.; Ali, L. M.; Vivet-Boudou, V.; Marquet, R.; Rizvi, T. A.
SHAPE analysis of the 5' end of the Mason-Pfizer monkey virus (MPMV) genomic RNA reveals structural elements required for genome dimerization Journal Article
In: Rna, vol. 19, no. 12, pp. 1648-58, 2013, ISSN: 1355-8382 (Print) 1355-8382.
@article{RN80,
title = {SHAPE analysis of the 5' end of the Mason-Pfizer monkey virus (MPMV) genomic RNA reveals structural elements required for genome dimerization},
author = {S. J. Aktar and A. Jabeen and L. M. Ali and V. Vivet-Boudou and R. Marquet and T. A. Rizvi},
doi = {10.1261/rna.040931.113},
issn = {1355-8382 (Print) 1355-8382},
year = {2013},
date = {2013-01-01},
urldate = {2013-01-01},
journal = {Rna},
volume = {19},
number = {12},
pages = {1648-58},
abstract = {Earlier genetic and structural prediction analyses revealed that the packaging determinants of Mason Pfizer monkey virus (MPMV) include two discontinuous core regions at the 5' end of its genomic RNA. RNA secondary structure predictions suggested that these packaging determinants fold into several stem-loops (SLs). To experimentally validate this structural model, we employed selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), which examines the flexibility of the RNA backbone at each nucleotide position. Our SHAPE data validated several predicted structural motifs, including U5/Gag long-range interactions (LRIs), a stretch of single-stranded purine (ssPurine)-rich region, and a distinctive G-C-rich palindromic (pal) SL. Minimum free-energy structure predictions, phylogenetic, and in silico modeling analyses of different MPMV strains revealed that the U5 and gag sequences involved in the LRIs differ minimally within strains and maintain a very high degree of complementarity. Since the pal SL forms a helix loop containing a canonical "GC" dyad, it may act as a RNA dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Analyses of wild-type and pal mutant RNAs revealed that disruption of pal sequence strongly affected RNA dimerization. However, when in vitro transcribed trans-complementary pal mutants were incubated together showed RNA dimerization was restored authenticating that the pal loop (5'-CGGCCG-3') functions as DIS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Earlier genetic and structural prediction analyses revealed that the packaging determinants of Mason Pfizer monkey virus (MPMV) include two discontinuous core regions at the 5' end of its genomic RNA. RNA secondary structure predictions suggested that these packaging determinants fold into several stem-loops (SLs). To experimentally validate this structural model, we employed selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), which examines the flexibility of the RNA backbone at each nucleotide position. Our SHAPE data validated several predicted structural motifs, including U5/Gag long-range interactions (LRIs), a stretch of single-stranded purine (ssPurine)-rich region, and a distinctive G-C-rich palindromic (pal) SL. Minimum free-energy structure predictions, phylogenetic, and in silico modeling analyses of different MPMV strains revealed that the U5 and gag sequences involved in the LRIs differ minimally within strains and maintain a very high degree of complementarity. Since the pal SL forms a helix loop containing a canonical "GC" dyad, it may act as a RNA dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Analyses of wild-type and pal mutant RNAs revealed that disruption of pal sequence strongly affected RNA dimerization. However, when in vitro transcribed trans-complementary pal mutants were incubated together showed RNA dimerization was restored authenticating that the pal loop (5'-CGGCCG-3') functions as DIS.
Saeed, I. A.; Ali, L.; Jabeen, A.; Khasawneh, M.; Rizvi, T. A.; Ashraf, S. S.
Estrogenic activities of ten medicinal herbs from the Middle East Journal Article
In: J Chromatogr Sci, vol. 51, no. 1, pp. 33-9, 2013, ISSN: 0021-9665.
@article{RN54,
title = {Estrogenic activities of ten medicinal herbs from the Middle East},
author = {I. A. Saeed and L. Ali and A. Jabeen and M. Khasawneh and T. A. Rizvi and S. S. Ashraf},
doi = {10.1093/chromsci/bms101},
issn = {0021-9665},
year = {2013},
date = {2013-01-01},
urldate = {2013-01-01},
journal = {J Chromatogr Sci},
volume = {51},
number = {1},
pages = {33-9},
abstract = {Traditional medicinal plants have long been recognized as remedies and important sources of treatment for developing countries. In the present study, we report on a detailed study to quantify the presence of five known phytoestrogens in 10 widely used herbs used in the Middle East. Surprisingly some of these plants were almost devoid of tested phytoestrogens, whereas others were very rich in known phytoestrogens. For example, Hibiscus sabdariffa was found to be the richest in quercetin and daidzein, whereas Cyperus conglomeratus had the highest concentrations of kaempferol and genistein. On the other hand, Salvadora persica was almost devoid of the screened phytoestrogens. Ethanolic extracts were further tested for their proliferative activities in cell-culture using estrogen-responsive breast cancer cell lines (MCF-7) and were found to fall into three distinct groups based on their estrogenic activities. The most potent herbal extract (O. vulgare) was further fractionated and the fractions were analyzed again for phytoestrogenic content (using high-performance liquid chromatography) and proliferative activity. Our results indicate that the proliferative activities of some of the extracts and fractions are not completely attributable to the phytoestrogens screened, thus it is likely that some of these plants may have other (perhaps yet unknown) phytoestrogens.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Traditional medicinal plants have long been recognized as remedies and important sources of treatment for developing countries. In the present study, we report on a detailed study to quantify the presence of five known phytoestrogens in 10 widely used herbs used in the Middle East. Surprisingly some of these plants were almost devoid of tested phytoestrogens, whereas others were very rich in known phytoestrogens. For example, Hibiscus sabdariffa was found to be the richest in quercetin and daidzein, whereas Cyperus conglomeratus had the highest concentrations of kaempferol and genistein. On the other hand, Salvadora persica was almost devoid of the screened phytoestrogens. Ethanolic extracts were further tested for their proliferative activities in cell-culture using estrogen-responsive breast cancer cell lines (MCF-7) and were found to fall into three distinct groups based on their estrogenic activities. The most potent herbal extract (O. vulgare) was further fractionated and the fractions were analyzed again for phytoestrogenic content (using high-performance liquid chromatography) and proliferative activity. Our results indicate that the proliferative activities of some of the extracts and fractions are not completely attributable to the phytoestrogens screened, thus it is likely that some of these plants may have other (perhaps yet unknown) phytoestrogens.
2010
Jaballah, S. A.; Aktar, S. J.; Ali, J.; Phillip, P. S.; Dhaheri, N. S. Al; Jabeen, A.; Rizvi, T. A.
In: J Mol Biol, vol. 401, no. 5, pp. 996-1014, 2010, ISSN: 0022-2836.
@article{RN42,
title = {A G-C-rich palindromic structural motif and a stretch of single-stranded purines are required for optimal packaging of Mason-Pfizer monkey virus (MPMV) genomic RNA},
author = {S. A. Jaballah and S. J. Aktar and J. Ali and P. S. Phillip and N. S. Al Dhaheri and A. Jabeen and T. A. Rizvi},
doi = {10.1016/j.jmb.2010.06.043},
issn = {0022-2836},
year = {2010},
date = {2010-01-01},
urldate = {2010-01-01},
journal = {J Mol Biol},
volume = {401},
number = {5},
pages = {996-1014},
abstract = {During retroviral RNA packaging, two copies of genomic RNA are preferentially packaged into the budding virus particles whereas the spliced viral RNAs and the cellular RNAs are excluded during this process. Specificity towards retroviral RNA packaging is dependent upon sequences at the 5' end of the viral genome, which at times extend into Gag sequences. It has earlier been suggested that the Mason-Pfizer monkey virus (MPMV) contains packaging sequences within the 5' untranslated region (UTR) and Gag. These studies have also suggested that the packaging determinants of MPMV that lie in the UTR are bipartite and are divided into two regions both upstream and downstream of the major splice donor. However, the precise boundaries of these discontinuous regions within the UTR and the role of the intervening sequences between these dipartite sequences towards MPMV packaging have not been investigated. Employing a combination of genetic and structural prediction analyses, we have shown that region "A", immediately downstream of the primer binding site, is composed of 50 nt, whereas region "B" is composed of the last 23 nt of UTR, and the intervening 55 nt between these two discontinuous regions do not contribute towards MPMV RNA packaging. In addition, we have identified a 14-nt G-C-rich palindromic sequence (with 100% autocomplementarity) within region A that has been predicted to fold into a structural motif and is essential for optimal MPMV RNA packaging. Furthermore, we have also identified a stretch of single-stranded purines (ssPurines) within the UTR and 8 nt of these ssPurines are duplicated in region B. The native ssPurines or its repeat in region B when predicted to refold as ssPurines has been shown to be essential for RNA packaging, possibly functioning as a potential nucleocapsid binding site. Findings from this study should enhance our understanding of the steps involved in MPMV replication including RNA encapsidation process.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
During retroviral RNA packaging, two copies of genomic RNA are preferentially packaged into the budding virus particles whereas the spliced viral RNAs and the cellular RNAs are excluded during this process. Specificity towards retroviral RNA packaging is dependent upon sequences at the 5' end of the viral genome, which at times extend into Gag sequences. It has earlier been suggested that the Mason-Pfizer monkey virus (MPMV) contains packaging sequences within the 5' untranslated region (UTR) and Gag. These studies have also suggested that the packaging determinants of MPMV that lie in the UTR are bipartite and are divided into two regions both upstream and downstream of the major splice donor. However, the precise boundaries of these discontinuous regions within the UTR and the role of the intervening sequences between these dipartite sequences towards MPMV packaging have not been investigated. Employing a combination of genetic and structural prediction analyses, we have shown that region "A", immediately downstream of the primer binding site, is composed of 50 nt, whereas region "B" is composed of the last 23 nt of UTR, and the intervening 55 nt between these two discontinuous regions do not contribute towards MPMV RNA packaging. In addition, we have identified a 14-nt G-C-rich palindromic sequence (with 100% autocomplementarity) within region A that has been predicted to fold into a structural motif and is essential for optimal MPMV RNA packaging. Furthermore, we have also identified a stretch of single-stranded purines (ssPurines) within the UTR and 8 nt of these ssPurines are duplicated in region B. The native ssPurines or its repeat in region B when predicted to refold as ssPurines has been shown to be essential for RNA packaging, possibly functioning as a potential nucleocapsid binding site. Findings from this study should enhance our understanding of the steps involved in MPMV replication including RNA encapsidation process.