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3 publications mentioning dme-mir-980

Open access articles that are associated with the species Drosophila melanogaster and mention the gene name mir-980. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

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[+] score: 278
This miRNA -based regulation was miR-980-specific, since overexpression of other miRNAs that are not predicted to target Rbfox1 (miR-966 and miR-278) did not result in the downregulation of the luciferase reporter containing Rbfox1 3′UTR (Fig.   1b, Supplementary Table  2). [score:9]
To identify predicted miR-980 targets in Drosophila, TargetScanFly Release 6.0 was used, and to identify miRNAs that putatively target human RBFOX family proteins, TargetScanHuman Release 7.0 was applied. [score:9]
Stress-responsive miR-980 targets Rbfox1 in vitro and in ovaries Drosophila miR-980 was previously identified as stress-linked in a screen for miRNAs that are differentially expressed in response to stress and disease [17]. [score:7]
Using the miRNA target prediction database TargetScan [34], we found three predicted conserved target sites for miR-980 in the 3′UTR of Rbfox1 mRNA. [score:7]
The following alleles were used to deregulate miR-980 expression: CG3777 [NP3544] (DGRC, previously described [17] as a hypomorphic mutation in the miR-980 gene and referred in the current study as miR-980 [NP3544]), miR-980 [KO] [33], miR-980 [Ex2], miR-980 [Ex1-1], miR-980 [Ex1-2], miR-980 [Ex1-3] (identical mutations generated in current study, Supplementary Figure  1, see below), and UAS-miR-980-dsRed [65]. [score:6]
d Nutritional stress (2-day) influences miR-980 and Rbfox1 expression in ovaries: miR-980 is significantly downregulated, while Rbfox1 is elevated. [score:6]
Since Rbfox1 levels globally influence RNA granule dynamics, we propose that the cell survival and differentiation defects observed as a result of Rbfox1 up- or down-regulation could be caused by Rbfox1 function as a liquid droplet-assembling LCD-containing protein Furthermore, Rbfox1 phase-separation and RNP granule formation is concentration dependent, since Rbfox1 aggregates more often under conditions that increase its cellular levels, such as miR-980 deficiency or stress, as well as Rbfox1 overexpression. [score:6]
We found the expression of both reporters to be substantially reduced upon miR-980 overexpression in S2R+ cells (Fig.   1b, Supplementary Table  2). [score:5]
To rescue the miR-980 loss of function phenotype by Rbfox1 downregulation, we introduced one copy of Rbfox1 mutation (Rbfox1 [EN403] /+) in the miR-980 [Ex1-2] homozygous background. [score:5]
In general, Pacman expression levels and the assembly of Pacman -positive P-bodies were enhanced upon Rbfox1 level increase achieved by miR-980 loss and starvation stress (Fig.   6b, c), showing that the increase in Rbfox1 expression positively affects P-body formation. [score:5]
Drosophila miR-980 was previously identified as stress-linked in a screen for miRNAs that are differentially expressed in response to stress and disease [17]. [score:5]
b miR-980 overexpression significantly reduces expression of luciferase reporters (P1 and P2), containing parts of the extended Rbfox1 3′UTR with different miR-980 binding sites. [score:5]
miR-980 was found to be downregulated upon various stresses (Supplementary Table  1), suggesting that it could play a role in stress tolerance. [score:4]
Since miR-980 deficiency results in higher Rbfox1 levels, we analyzed the consequence of miR-980-insensitive Rbfox1 isoform upregulation in follicle cell clones upon stress. [score:4]
Among these, Rbfox1 ~50 kDa isoform was specifically upregulated upon miR-980 loss (Fig.   1e, Supplementary Figure  3A). [score:4]
At the same time, an Rbfox1 isoform that runs at ~110 kDa was upregulated in controls and miR-980 mutants only upon starvation, while ~60 kDa isoform levels did not show any significant fluctuations at different conditions and in the studied genotypes (Fig.   1e, Supplementary Figure  3A). [score:4]
Therefore, we wanted to address how important is the presence of alternative 3′UTRs, thus, targeting of Rbfox1 by miR-980, and what effect this regulation has on cellular status. [score:4]
To test what happens if Rbfox1 is not subjected to miR-980 -based regulation, we analyzed mutants overexpressing one of the Rbfox1 isoforms lacking the extended 3′UTR (Rbfox1-RE, Supplementary Figure  2B). [score:4]
Delayed termination of egg production in miR-980 mutants is rescued by Rbfox1 downregulation. [score:4]
In summary, these data show that upon starvation, the regulation of Rbfox1 expression is partially achieved via stress -dependent miR-980 -based buffering and that increased Rbfox1 levels modulate cell growth, differentiation, autophagy, and apoptosis. [score:4]
In miR-980 mutants, elevated Rbfox1 levels were detected at all developmental stages (Fig.   1g), demonstrating that miR-980 is responsible for the control of the highly dynamic Rbfox1 expression during the entire process of oogenesis. [score:4]
Moreover, higher Rbfox1 levels were detected in both sated and starved miR-980 mutant ovaries, and this upregulation was isoform-specific (Supplementary Figure  3A, Fig.   1e). [score:4]
miR-980 can target Rbfox1 cell-autonomously, since its clonal overexpression in the ovarian follicular epithelium resulted in the reduction of Rbfox1 protein levels compared to neighboring wild type cells (Supplementary Figure  3B,D). [score:4]
Upon stress, miR-980 levels are reduced, causing Rbfox1 upregulation and promoting cell survival. [score:4]
Rbfox1 upregulation in miR-980 mutants modifies nucleolar shape and size. [score:4]
Notably, we also found that only a part of Rbfox1 mRNA could be subjected to miR-980 -based regulation, since only a part of Rbfox1 transcripts have the extended 3′UTRs containing miR-980 target sites. [score:4]
To quantitate Rbfox1 protein levels in wild type (Oregon R), miR-980 mutant, and Rbfox1 -overexpressing (hsFlp; act> CD2> Gal4 UAS-GFP/UAS-Rbfox1RE, heat shocked 1 h for two consecutive days at the pupal stage) ovaries, animals were kept either at normal (apple juice plates with yeast paste supplement) or protein starvation (apple juice only plates) food conditions for 3 days prior to dissection. [score:3]
Then, verified miR-980 mutant males (w,P [Ex] />;+;+) with no changes in the expression of CG3777 were crossed to females carrying an FM7 balancer chromosome to obtain homozygous stocks. [score:3]
Our results show that a miRNA, miR-980, and its target, Rbfox1, interact to have a profound effect on cell survival, growth, and differentiation, and subsequently, on organismal viability upon stress. [score:3]
Since miR-980 mutants showed abnormal response to starvation (Fig.   1a), next, we analyzed whether miR-980 targeting of Rbfox1 has a functional role in the dietary stress response. [score:3]
miR-980 buffers Rbfox1 levels, since it can target only the portion of Rbfox1 transcripts that contain extended 3′UTRs. [score:3]
Even more, overexpression of miR-980-insensitive Rbfox1-PE isoform in the follicle cells had an effect on the nucleolar size and shape (Fig.   5b, c). [score:3]
The percentage of CBs that also co-stained with Rbfox1 was increased in miR-980 mutants that express higher Rbfox1 levels (Fig.   5e). [score:3]
e Rbfox1 levels in wild type (WT), miR-980, and Rbfox1 -overexpressing (hsFlp; act > CD2 > Gal4 UAS-GFP/UAS-Rbfox1-RE) ovaries from sated and protein-deprived animals detected by western blotting. [score:3]
To test if miR-980 targets Rbfox1 via the predicted miRNA binding sites, we cloned different Rbfox1 3′UTR regions containing miR-980 binding sites into luciferase reporters (P1 and P2, Supplementary Figure  2D). [score:3]
Altogether, these data show that stress and miR-980 affect Rbfox1 expression at the mRNA and protein levels. [score:3]
miR-980 can target only the portion of Rbfox1 mRNAs with the alternative extended 3′UTRs. [score:3]
Reduced miR-980 expression during stress leads to increased Rbfox1 levels, followed by widespread formation of RNP granules, promoting cell survival. [score:3]
We found that miR-980 is expressed in the ovarian germline and soma (Supplementary Figure  1E, F). [score:3]
Stress-responsive miR-980 targets Rbfox1 in vitro and in ovaries. [score:3]
The abundance of these structures was increased in miR-980 mutants (Fig.   4b), which, as we have shown above, express higher Rbfox1 levels. [score:3]
Next, male flies were used to test expression levels of miR-980 and CG3777 by qRT-PCR. [score:3]
In addition, similar to the starved S2R+ cells overexpressing Rbfox1-PE (Fig.   3f), notable long filamentous structures were observed in stressed miR-980 ovaries (Fig.   4c, d). [score:3]
To generate follicle cell clones expressing Rbfox1, Rbfox1 [RNAi], or miR-980, females of the genotype hsFlp; act> CD2> Gal4 UAS-GFP were mated with males of genotypes UAS-miR-980 or UAS-Rbfox1. [score:3]
This association with the nucleolus and CBs becomes more pronounced under conditions that lead to increased Rbfox1 expression, such as miR-980 loss or starvation stress. [score:3]
Rbfox1 mRNA has the possibility of having alternative 3′UTRs – two short and two long 3′UTRs – and all three conserved miR-980 target sites are found only in the alternative extended 3′UTR (Supplementary Figure  2C, D). [score:3]
Moreover, miR-980 deficiency and Rbfox1 overexpression caused changes in nucleolar morphology, as higher percentages of nucleoli appeared to have an inkblot-like shape or to be more segregated and dispersed in mutants in comparison to controls (Fig.   5a, b). [score:3]
We used plasmids expressing miR-980, miR-966 and miR-278 miRNAs. [score:3]
Guven-Ozkan T MiR-980 is a memory suppressor MicroRNA that regulates the autism-susceptibility gene A2bp1Cell Rep. [score:3]
miR-980 and Rbfox1 expression depends on stress: miR-980 levels are substantially reduced, while Rbfox1 mRNA levels are increased in response to metabolic stress (Fig.   1d, Supplementary Tables  1 and 3). [score:3]
In particular, Rbfox1 isoforms that migrated at ~50 kDa, ~65 kDa, ~75 kDa, and ~120 kDa showed increased expression levels in miR-980 mutants in comparison to controls at normal conditions (Fig.   1e). [score:3]
Similarly, in the cytoplasm, the appearance of Rbfox1 -positive granules depends on both stress and miR-980 -based Rbfox1 regulation (Fig.   5e–g). [score:2]
This suggests that Rbfox1 is required for ovarian cell differentiation, and it would be unfavorable for all Rbfox1 isoforms to be subjected to miR-980 regulation. [score:2]
Stress -dependent miR-980 regulates Rbfox1, amending cell survival. [score:2]
Similar to in vitro results, in vivo, Rbfox1 mRNA levels in ovaries were increased upon miR-980 loss, confirming that miR-980 regulates Rbfox1 during oogenesis (Fig.   1c, Supplementary Table  3). [score:2]
Selected miR-980 loss of function mutants (miR-980 [Ex2]; miR-980 [Ex1-1]; miR-980 [Ex1-2]; miR-980 [Ex1-3]) were used for mapping of miR-980 mutations. [score:2]
Recently, the miR-980/ Rbfox1 interaction in the adult Drosophila brain has also been shown to regulate memory via the modulation of calcium responses [20], further demonstrating the wide range of physiological processes dependent on miR-980/ Rbfox1 interaction. [score:2]
In miR-980 mutant ovaries, Rbfox1 protein levels as well as the size and number of Rbfox1 -positive aggregates were apparently increased at all developmental stages in the germline and somatic cells (Figs.   1f, g, 5a, Supplementary Figure  6). [score:2]
For example, by varying the length of the 3′UTR, Rbfox1 becomes more or less accessible for regulation by miRNAs, including miR-980. [score:2]
of one copy of Rbfox1 mutation to the miR-980 loss-of-function background rescues the phenotype. [score:2]
Mapping of miR-980 mutations. [score:2]
Mapping of miR-980 mutationsTo map generated miR-980 loss of function mutants, genomic DNA samples from males of the genotypes (1) w [1118], positive control, (2) CG3777 [NP3544], negative control and (3) miR-980 loss of function mutants were isolated using QIAGEN DNEasy Blood and Tissue Kit, following the manufacturer’s protocol. [score:2]
Rbfox1 has previously been implicated in ovarian germline differentiation; moreover, recently it has been shown that Rbfox1 is regulated by miR-980 in the process of memory formation 18– 20. [score:2]
However, in miR-980 mutants, Rbfox1 association with the nucleolus is even more evident (yellow in Fig.   5a). [score:1]
First, we tested Rbfox1 protein levels in ovarian lysates from sated and starved wild type and miR-980 mutant animals. [score:1]
This tendency becomes even more pronounced upon starvation stress (n = 598 and 262 CBs for miR-980 and Control, respectively). [score:1]
b, c Upon miR-980 loss or starvation, which leads to elevated Rbfox1 levels, the appearance of P-bodies increases. [score:1]
c, d Sometimes, Rbfox1 can form various phase-separated long fibers in both germline (c lower panel) and somatic follicle cells (d) of miR-980 mutants. [score:1]
Rbfox1 RE isoform has a shortened 3′UTR that lacks miR-980 binding sites. [score:1]
Second, the amount and the solubility of SDS-resistant Rbfox1 -positive aggregates were condition -dependent, suggesting that the increase in Rbfox1 levels due to stress and miR-980 loss promotes the formation of Rbfox1 aggregates and their transition into a less soluble, possibly amyloid-like state. [score:1]
e Rbfox1 association with CBs is enhanced by miR-980 loss and stress. [score:1]
We show that Rbfox1 levels are adjusted by the stress-sensitive miRNA, miR-980, which significantly influences the stress response. [score:1]
Fig. 1Rbfox1 levels depend on miR-980 and stress. [score:1]
The ΔCT value was determined by subtracting the average RpL32 or Act5c CT value from the average Rbfox1 and CG3777 CT value or the average 2S rRNA CT value from the average miR-980 CT value. [score:1]
The delay in the termination of egg production upon starvation caused by miR-980 deficiency can be fully rescued by the reduction of the Rbfox1 gene by one copy (Fig.   1h, i). [score:1]
To generate miR-980 loss of function mutants, the excision of the P-element P GawB CG3777 [NP3544] (DGRC) was induced. [score:1]
For the, miRCURY LNA probe was ordered from Exiqon (dme- miR-980 product # 21455-15). [score:1]
h Assembly of Control and miR-980 ovarioles under normal and starvation stress conditions. [score:1]
9-10 follicular epithelial cells (n = 273 cells for Control, 234 for miR-980 [Ex1-2] and 92 for Rbfox1 OE). [score:1]
Generation of Drosophila miR-980 mutantsTo generate miR-980 loss of function mutants, the excision of the P-element P GawB CG3777 [NP3544] (DGRC) was induced. [score:1]
To generate the Rbfox1-3′UTR sensors, a 381 bp region (P1) and a 396 bp region (P2) containing the putative miR-980 binding sites were amplified from genomic Drosophila melanogaster DNA by polymerase chain reaction (Supplementary Figure  2D). [score:1]
g In miR-980 [Ex1-2], Rbfox1 is elevated in comparison to Control egg chambers of the corresponding stages. [score:1]
j Scheme represents miR-980/Rbfox1 function in response to nutritional stress. [score:1]
f Percentages of Rbfox1 -positive CBs are significantly increased in miR-980 mutants in comparison to Control (n = 82 and 256 CBs, respectively). [score:1]
We prepared ovarian lysates from wild type and miR-980 -deficient animals that were well-fed or starved. [score:1]
We found that Rbfox1 assembles even longer fiber-like structures in the nuage of starved miR-980 mutants (Fig.   5g, yellow arrow). [score:1]
Similarly, in the germline, Rbfox1 colocalized with CBs (Fig.   5g, blue arrowheads) and the size and the number of CBs were increased in the starved and miR-980 -deficient ovaries. [score:1]
c miR-980 ovaries have significantly increased Rbfox1 mRNA levels. [score:1]
In addition, we found that colocalization of Rbfox1 with the CB marker, Coilin, depends on the presence of miR-980. [score:1]
Images of sated and 10-day protein-starved Control and miR-980 ovaries. [score:1]
Since upon stress or miR-980 loss, the levels of Rbfox1 generally increase, this, via LCD -mediated interactions, stimulates aggregation of other LCD-containing proteins that have specific functions in the nuclear and cytoplasmic liquid organelles. [score:1]
The Rbfox1 gene encodes different isoforms (Supplementary Figure  2A, B) that also differ by the 3′UTR choice, and only the extended 3′UTRs (medium and long) contain miR-980 binding sites (Supplementary Figure  2C, D). [score:1]
Therefore, turning miR-980 “on” in a timely fashion could potentially prevent toxic fiber formation. [score:1]
The amount of Rbfox1 -positive aggregates detected by the SDD-AGE was dependent on stress and miR-980 presence, since the increase in Rbfox1 aggregations was observed in starved control and in well-fed and starved miR-980 mutant ovaries in comparison to well-fed controls (Fig.   3b, experiment). [score:1]
In addition, Rbfox1 isoform specificity is adjusted by stress and miR-980 deficiency. [score:1]
Interestingly, Drosophila miR-980 is related to the miR-22 family in humans and that human RBFOX2 has a predicted binding site for miR-22 (Supplementary Table  7). [score:1]
In starved miR-980 mutants, Rbfox1 -positive fibers can be observed (yellow arrows, right panel). [score:1]
This demonstrates that the miR-980 diet-sensitive ovarian phenotype is Rbfox1 -dependent and that the higher levels of Rbfox1 are beneficial for oogenesis progression upon nutritional stress. [score:1]
Similar Rbfox1 -positive, elongated assemblies were also seen in the somatic follicle cells at late oogenesis stages in wild type and miR-980 deficient animals (st. [score:1]
Generation of Drosophila miR-980 mutants. [score:1]
g In the germline, Rbfox1 colocalizes with CBs (blue arrowheads) and this colocalization is enhanced by miR-980 loss and stress. [score:1]
Similarly, in the miR-980 -deficient germline, the appearance of the nucleoli in the nurse cells was changed in comparison to control nurse cells of the same stage (Supplementary Figure  6C–F). [score:1]
Starvation response is not as robust in miR-980 mutants, their ovaries are larger and contain later stage egg chambers. [score:1]
To map generated miR-980 loss of function mutants, genomic DNA samples from males of the genotypes (1) w [1118], positive control, (2) CG3777 [NP3544], negative control and (3) miR-980 loss of function mutants were isolated using QIAGEN DNEasy Blood and Tissue Kit, following the manufacturer’s protocol. [score:1]
Fig. 9The miR-980/Rbfox1 -mediated stress-responsive signaling cascade. [score:1]
Therefore, next, we used Drosophila oogenesis as an in vivo mo del to address miR-980 stress-related functions. [score:1]
Interestingly, miR-980 is shut down by any stress we tested: muscular dystrophy and aging [17], temperature, and starvation (this study). [score:1]
In response to different stresses or miR-980 loss, more Rbfox1 -positive granules could be detected in the cytoplasm (P-bodies and stress granules). [score:1]
a, b Upon prolonged protein starvation (1–3 weeks) in Control (a) and miR-980 (b) ovaries, Rbfox1 aggregates in cytoplasmic and nuclear droplets of various size and shape. [score:1]
This tendency was even more pronounced in miR-980 mutants, in which more than 80% of CBs were Rbfox1 -positive under stress (Fig.   5f). [score:1]
In addition, the ovaries of miR-980 mutants seemed to be enlarged, and their size did not decrease as apparently as in controls in response to starvation stress (Fig.   1a), suggesting that the miRNA miR-980 is involved in fine-tuning of the dietary stress response during oogenesis. [score:1]
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[+] score: 127
The downregulation of miR-980 in pupae relative to the expression levels at other life stages supports that miR-980 is ‘off’ to allow for higher levels of proteins necessary for metamorphic neurological remo deling. [score:6]
Statistics were done using a two-tailed Student’s t-test: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. miR-980 has mostly nervous system predicted targets and is expressed during embryogenesis and the larval stage, but a decrease in levels is seen in pupae (Figure  5c). [score:5]
P[GawB]CG3777 [NP3544] (P-element insert in the miR-980 gene resulting in a 70% reduction of expression, miR-980 hypomorph (Additional file 1), stock #113334) and PBac[SAstopDsRed]LL04028 (PiggyBac element inserted in the miR-252 gene resulting in no detectable expression, miR-252 amorph (Additional file 1), stock #140830) were obtained from the Kyoto Drosophila Genetic Resource Center. [score:5]
Statistics were done using a two-tailed Student’s t-test: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. miR-980 has mostly nervous system predicted targets and is expressed during embryogenesis and the larval stage, but a decrease in levels is seen in pupae (Figure  5c). [score:5]
Interestingly, miR-980 can potentially target Dg while Dg, Dys and Syn1 are putative miR-252 targets. [score:5]
Analysis of miR-980 expression shows that it is expressed in the developing eye, the axons of photoreceptor neurons and in the midbrain (Figure  5d). [score:5]
Since it has been found that the most robust mRNA targets of miRNAs can be detected by variation in mRNA levels [37, 38], we tested the putative DGC component and conserved muscle targets via RT q-PCR in miR-980 and miR-252 mutants. [score:5]
Conserved Drosophila targets were determined for miR-252, miR-956 and miR-980 using targetscan. [score:5]
An expression pattern similar to the expression of miR-980 is seen for miR-252 (Figure  5f). [score:5]
Here we have shown that miR-956, miR-980 and miR-252 are all downregulated in mutants with RNAi against Syn1 indicating that a comparable pathway is present in Drosophila that is not only present in muscle, but other tissues as well (i. e. the nervous system). [score:4]
The expression profiling and detection of miR-956, miR-980 and miR-252 supports our hypothesis that Dg-Dys-Syn1 signaling is part of an organism’s overall development and homeostasis. [score:4]
Note the reduced expression levels in miR-980 hypomorphs. [score:3]
miR-980 expression in the adult body could be from the peripheral nervous system including the thoracic ganglion, a large structure located in the thorax. [score:3]
In accord with the reduced miR-980 levels, miR-980 mutants have a reduced, but not abolished LNA hybridization signal (Figure  5d) which supports the specificity of miR-980 expression detected by the LNA probe. [score:3]
Because miR-956, miR-980 and miR-252 are predicted to be involved in varied processes and are regulated via the Dg-Dys-Syn1 pathway, we hypothesize that this signaling plays a role in general cellular processes of the nervous system and muscle via miRNA regulation. [score:3]
miR-980 expression was not detected in the larval body wall muscles. [score:3]
We found that miR-980, miR-956 and to a greater extent, miR-252 can potentially target a portion of them (Table  1). [score:3]
q-PCR analysis revealed the expression levels during all life stages and in adult body parts for (a) miR-956 (c) miR-980 and (e) miR-252. [score:3]
After careful analysis, miR-980 showed 24 putative target genes (Additional file 1) and the majority of them are involved in axon guidance (Figure  4b). [score:3]
Gene ontology predictions of putative (a) miR-252, (b) miR-980 and (c) miR-956 target genes. [score:3]
In adult animals, the dNOS transcript is found preferentially in heads, but not bodies [55], and the primary adult tissue that we see miR-252 and miR-980 expressed in is the adult head. [score:3]
The Dg-Dys-Syn1 regulated miR-980 is likely to be primarily involved in nervous system development tuning axon guidance. [score:3]
We additionally analyzed larval brains and muscles using Locked Nucleic Acid (LNA) in situ hybridization with probes targeting miR-956, miR-980 and miR-252. [score:3]
We found that similarities are shared in miRNA profiles under stress and dystrophic conditions, that loss of Dg and/or Dys can alter miRNA levels and that signaling via Syntrophin-like 1 (Syn1) controls the expression levels of miR-252, miR-956 and miR-980. [score:3]
This is particularly interesting since we did not detect miR-980 expression in muscle, but in the nervous system (Figure  5d). [score:3]
The regulation of miR-252 and miR-980 is not restricted to the musculature, but occurs also in the nervous system. [score:2]
miR-980 regulates stress response in Drosophila. [score:2]
We found that potential Dg-regulated miRNAs are miR-956, miR-962, miR-980, miR-274, miR-312, miR-975, and miR-1003. [score:2]
Verification of a subset of our results was conducted via q-PCR and revealed that miR-956, miR-980 and miR-252 are regulated via a Dystroglycan-Dystrophin-Syntrophin dependent pathway. [score:2]
Potential Dys-regulated miRNAs are miR-956, miR-252, miR-980, miR-124, miR-970, miR-283, miR-927, miR-iab-4-5p, miR-962, miR-959, and miR-975. [score:2]
We were particularly interested in Dys signaling miRNA regulation, thus we tested the “Dys Dependent” cluster from Figure  2d: miR-956, miR-252, miR-124, miR-970, miR-283, miR-927, miR-iab-4-5p, miR-962, miR-980, miR-959, and miR-975 (Additional file 1). [score:2]
miR-980 regulates stress response in DrosophilaAs can be seen in Figure  3d, miR-980 levels were also decreased due to hyperthermic stress. [score:2]
miR-956, miR-980 and miR-252 were found to be present in the nervous system and miR-956 is also present in the musculature. [score:1]
Interestingly, the reduction of miR-980 preserved the muscles after the same time period at 33°C relative to 25°C (Table  2, Figure  6a,b). [score:1]
These data suggest the miR-980 has a specific function in the nervous system that influences muscle functioning and subsequently longevity under hyperthermic stress. [score:1]
Dystrophic miRNAs revealed are miR-956, miR-980, miR-984, miR-975, miR-959, miR-iab-4-5p and miR-1003. [score:1]
Interestingly, appropriate levels of miR-252, miR-956 and miR-980 depend on both Dg and Dys (Figure  3d). [score:1]
We chose to examine the effect of Syn1 reduction via RNAi (dsSyn1) on the levels of miR-252, miR-956 and miR-980, since in mammals it was found that α1/β1/β2-syntrophins bind to nNOS [27]. [score:1]
Based on these results we hypothesize that the reduction of miR-980 under high temperature stress makes flies immobile, which is to some extent a protective mechanism that can at least preserve muscle tissue for a period of time. [score:1]
There can be two sub-categories delineated; miRNAs that do not change normally under stress, but do in dystrophic mutants (miR-92a and miR-34) and miRNAs that change as a normal response, but do not in Dys and Dg mutants (miR-956, miR-252, miR-970, miR-137, miR-986, miR-193, miR-1017, miR-962, miR-315, miR-1013, miR-980, miR-975, miR-190, miR-iab-4as-5p, miR-1003 and miR-313). [score:1]
The result is a hypomorphic homozygous viable mutant that reduces miR-980 levels by ~70% analyzed via RT q-PCR at the ambient temperature (Figure  5c). [score:1]
The Flybase annotated allele P[GawB]CG3777 [NP3544] disrupts miR-980, but does not disturb the mature sequence. [score:1]
Therefore, we next wanted to determine if miR-980 is involved in stress biology. [score:1]
Interestingly, the lifespan of miR-980 mutants at 25°C was similar to control and only at 33°C did they start dying significantly earlier than wt animals (50% lethality noted at 14.3 days vs. [score:1]
Once metamorphosis is complete, miR-980 levels are elevated again, and the highest relative level is noted in the head. [score:1]
miRCURY LNA probes were purchased from Exiqon that are complementary to Drosophila miR-956 (product # 21431–15), miR-980 (product # 21455–15) and miR-252 (product # 21423–15). [score:1]
As can be seen in Figure  3d, miR-980 levels were also decreased due to hyperthermic stress. [score:1]
Dg mRNA levels were not altered in hypomorphic miR-980 mutants (Figure  5g), but miR-980 levels are not completely abolished. [score:1]
The timing of this inability to move coincided with the onset when miR-980 mutants started to die (Table  2). [score:1]
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3
[+] score: 1
Other miRNAs from this paper: hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, dme-mir-1, dme-mir-8, dme-mir-11, hsa-mir-34a, hsa-mir-210, dme-mir-184, dme-mir-275, dme-mir-92a, dme-mir-276a, dme-mir-277, dme-mir-33, dme-mir-281-1, dme-mir-281-2, dme-mir-34, dme-mir-276b, dme-mir-210, dme-mir-92b, dme-bantam, dme-mir-309, dme-mir-317, hsa-mir-1-2, hsa-mir-184, hsa-mir-190a, hsa-mir-1-1, hsa-mir-34b, hsa-mir-34c, aga-bantam, aga-mir-1, aga-mir-184, aga-mir-210, aga-mir-275, aga-mir-276, aga-mir-277, aga-mir-281, aga-mir-317, aga-mir-8, aga-mir-92a, aga-mir-92b, hsa-mir-92b, hsa-mir-33b, hsa-mir-190b, dme-mir-190, dme-mir-957, dme-mir-970, dme-mir-981, dme-mir-927, dme-mir-989, dme-mir-252, dme-mir-1000, aga-mir-1174, aga-mir-1175, aga-mir-34, aga-mir-989, aga-mir-11, aga-mir-981, aga-mir-1889, aga-mir-1890, aga-mir-1891, aga-mir-190, aga-mir-927, aga-mir-970, aga-mir-957, aga-mir-1000, aga-mir-309, cqu-mir-1174, cqu-mir-281-1, cqu-mir-1, cqu-mir-275, cqu-mir-957, cqu-mir-277, cqu-mir-252-1, cqu-mir-970, cqu-mir-317-1, cqu-mir-981, cqu-mir-989, cqu-mir-1175, cqu-mir-276-1, cqu-mir-276-2, cqu-mir-276-3, cqu-mir-210, cqu-mir-92, cqu-mir-190-2, cqu-mir-190-1, cqu-mir-1000, cqu-mir-11, cqu-mir-8, cqu-bantam, cqu-mir-1891, cqu-mir-184, cqu-mir-1890, cqu-mir-980, cqu-mir-33, cqu-mir-2951, cqu-mir-2941-1, cqu-mir-2941-2, cqu-mir-2952, cqu-mir-1889, cqu-mir-309, cqu-mir-252-2, cqu-mir-281-2, cqu-mir-317-2, aga-mir-2944a-1, aga-mir-2944a-2, aga-mir-2944b, aga-mir-2945, aga-mir-33, aga-mir-980
We also observed changes in miR-957, miR-970, miR-980, and miR-33, among others (Additional file 2, Table S1). [score:1]
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