Identification of miR-305, a microRNA that promotes ageing, and its target mRNAs in Drosophila
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE107158 | GEO | 2018/02/14
REPOSITORIES: GEO
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Project description:It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMP) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild type flies to survive much better in hyperoxia. In the current study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with antimicrobial peptide overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS level after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that a) AMPs play an important role in tolerance to oxidant stress; b) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and c) this change in redox balance plays an important role in survival in hyperoxia. Expression profiles of Drosophila melanogaster with anti-microbial peptide over-expression (experimental sample; n=3) and controls (UAS-AMP alone not crossed to da-GAL4; n=3) were determined using Affymetrix Drosophila Genome 2.0 Arrays.
2010-12-21 | E-GEOD-23902 | biostudies-arrayexpress
Project description:It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMP) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild type flies to survive much better in hyperoxia. In the current study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with antimicrobial peptide overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS level after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that a) AMPs play an important role in tolerance to oxidant stress; b) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and c) this change in redox balance plays an important role in survival in hyperoxia.
2010-12-21 | GSE23902 | GEO
Project description:Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.
2019-11-12 | PXD009845 | Pride
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir378_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110002.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110002 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mir181_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110001.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110001 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mir143_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110003.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110003 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mirs_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Nature Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110004.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110004 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir1_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Nature Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110000 | BioModels
Project description:Identification of miR-305, a microRNA that promotes ageing, and its target mRNAs in Drosophila
| PRJNA419195 | ENA
Project description:The Toll signaling pathway is highly conserved from insects to mammals. Drosophila is a model species that is commonly used to study innate immunity. Although many studies have assessed protein-coding genes that regulate the Toll pathway, it is unclear whether long noncoding RNAs (lncRNAs) play regulatory roles in the Toll pathway. Here, we evaluated the expression of the lncRNA CR46018 in Drosophila. Our results showed that this lncRNA was significantly overexpressed after infection of Drosophila with Micrococcus luteus. A CR46018-overexpressing Drosophila strain was then constructed; we expected that CR46018 overexpression would enhance the expression of various antimicrobial peptides downstream of the Toll pathway, regardless of infection with M. luteus. RNA-seq analysis of CR46018-overexpressing Drosophila after infection with M. luteus showed that upregulated genes were mainly enriched in Toll and Imd signaling pathways. Moreover, bioinformatics predictions and RNA-immunoprecipitation experiments showed that CR46018 interacted with the transcription factors Dif and Dorsal to enhance the Toll pathway. During gram-positive bacterial infection, flies overexpressing CR46018 showed favorable survival compared with flies in the control group. Based on these findings, we renamed CR46018 as lncRNA-RDIP. Overall, our current work not only reveals a new immune regulatory factor, lncRNA-RDIP, and explores its potential regulatory model, but also provides a new perspective for the effect of immune disorders on the survival of Drosophila melanogaster.
2021-05-20 | GSE174684 | GEO