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9 publications mentioning dre-mir-196a-2

Open access articles that are associated with the species Danio rerio and mention the gene name mir-196a-2. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 199
In this study we identified a miRNA (miR-196a) targeting bovine NOBOX, examined the temporal expression of miR-196a during bovine early embryonic development and determined the effect and specificity of miR-196a in regulating bovine NOBOX expression both exogenously (HeLa cells) and endogenously in early embryos. [score:9]
Since we determined in heterologous systems that miR-196a is capable of regulating NOBOX expression through direct binding to the 3' UTR of its mRNA, the ability of miR-196a to regulate endogenous NOBOX expression in early embryos was determined. [score:8]
In order to examine if miR-196a expression is inversely correlated to bovine NOBOX expression during early embryonic development, we analyzed miR-196 expression during oocyte maturation and early embryogenesis. [score:8]
Moreover, when the spatio-temporal expression pattern of miR-196a is compared with the expression pattern of bovine NOBOX during early embryogenesis, miR-196a expression increases steadily from two-cell to eight-cell stage of embryogenesis, while NOBOX expression decreases gradually during the same period [29]. [score:8]
A significant inhibition of NOBOX expression was observed in HeLa cells ectopically expressing both NOBOX and miR-196a (Figure 3A) relative to cells transfected with NOBOX alone. [score:7]
Furthermore, miR-196a regulates mammalian development via targeting homoeobox clusters [22] and misexpression of miR-196a leads to specific eye anomalies in a dose -dependent manner in Xenopus laevis [23]. [score:7]
Similarly, the activity of a luciferase construct containing the entire 3' UTR of bovine NOBOX was suppressed, and the regulation was abolished by mutations in the miR-196a binding site indicating that the predicted MRE is critical for the direct and specific binding of miR-196a to the NOBOX mRNA. [score:6]
Collectively, our results demonstrate the ability of miR-196a to negatively regulate NOBOX expression in a sequence specific fashion and the ability of miR-196a to suppress NOBOX mRNA and protein in early embryos. [score:6]
Expression analysis of miR-196a in bovine oocytes and during early embryonic development indicated that it is expressed both in oocytes and embryos and tends to increase at the four-cell and eight-cell stages. [score:6]
Ectopic expression of NOBOX and miR-196a in HeLa cells inhibited the expression of NOBOX protein compared to the control cells without miR-196a. [score:6]
Semi-quantitative analysis of western blot data showed a significant inhibition of NOBOX expression in the miR-196a -transfected cells (Figure 3B). [score:5]
Ectopic expression of miR-196a by transfection of miR-196a duplex into the HeLa cells suppressed activity of a chimeric luciferase construct containing the miR-196a MRE of NOBOX at its 3' end (Figure 4B). [score:5]
miR-196a specifically suppresses the expression of bovine NOBOX. [score:5]
The involvement of miR-196a in regulating the expression of NOBOX supports a new role of this miRNA in early embryonic development during MET. [score:5]
Furthermore, ectopic expression of miR-196a mimic in bovine early embryos significantly reduced the NOBOX expression at the both mRNA and protein levels. [score:5]
Figure 3Regulation of bovine NOBOX expression by miR-196a in vitro in HeLa cells. [score:4]
In addition, when the NOBOX sequence was analyzed with other miRNA target prediction algorithms, miR-196a always was listed as a top candidate miRNA, further indicating that miRNA-196a might be a potential post-transcriptional regulator of NOBOX in early embryos. [score:4]
Recent studies showed that 75% of tumors express high levels of miR-196a and miR-196a is involved in regulating key pathways such as AKT signaling, p53 and WNT signaling pathways [49, 50]. [score:4]
It has also been reported that miR-196a is differently regulated during polycystic kidney disease suggesting that miR-196 is important for normal functioning of kidney [51]. [score:4]
Thus, the inverse relationship between miR-196a and NOBOX expression/activity supports the proposed role of miR-196a as a physiological regulator of NOBOX during early embryogenesis. [score:4]
Figure 4 miR-196a specifically binds to the 3' UTR of bovine NOBOX and regulates its expression. [score:4]
Ectopic expression of miR-196a mimic in bovine embryos effectively reduced NOBOX protein expression in eight-cell embryos compared to uninjected and the negative control miRNA -injected embryos (Figure 5A). [score:4]
Thus, a similar mechanism is likely to be involved in the miR-196a negative regulation of NOBOX expression in bovine embryos during MET. [score:4]
Moreover, recent studies support a functional role for this specific miRNA as miR-196a targets specific homeobox genes (HoxB8, HoxC8, HoxD8 and HoxA7) in mouse embryos and mammalian cells and plays a major role in animal development [22]. [score:4]
Mutation of the mir-196a miRNA recognition element (MRE) in the NOBOX 3' UTR was performed using the QuickChange site-directed mutagenesis kit (Stratagene, Santaclara, CA) according to the manufacturer's instructions. [score:3]
These results unequivocally show that bovine NOBOX is regulated at the post-transcriptional level by miR-196a and further supports the hypothesis that miR-196a is responsible for the negative regulation of NOBOX. [score:3]
Expression analysis indicates that bovine miR-196a is increased in four-cell and eight-cell stage embryos relative to germinal vesicle stage oocytes and declines at morula and blastocyst stages (Figure 2B). [score:3]
The increased expression level of miR-196a near the eight-cell stage of embryogenesis potentially indicates miR-196a involvement in maternal transcript degradation during the maternal-to-zygotic transition, as was observed for miR-430 in zebrafish [10] miR-427 in Xenopus [38] and miR-290 in mouse [20]. [score:3]
Figure 2 Spatial and temporal expression profile of miR-196a. [score:3]
As shown in Figure 2A, miR-196a is expressed predominantly in kidney; it is also detected significantly in fetal and adult ovary, brain and hypothalamus. [score:3]
miR-196a is spatio-temporally regulated during development. [score:3]
A similar expression pattern was observed in mice where miR-196a is enriched in the kidney and adult reproductive tissues [37]. [score:3]
The relative amount of miR-196a was expressed as relative fold change using the sample with the lowest value as the calibrator (n = 4, mean ± SEM). [score:3]
Nucleotides changed to generate the target site mutant 3' UTR are underlined (B) Repression of luciferase activity due to specific interaction between miR-196a and the predicted MRE in the luciferase-NOBOX-3' UTR constructs. [score:3]
Figure 5 Microinjection of miR-196a mimic represses endogenous NOBOX expression in bovine early embryos. [score:3]
Quantity of miRNA-196a was normalized to abundance of RPS18 mRNA and abundance expressed as relative fold change using the sample with the lowest value as the calibrator (n = 4 per tissue; mean ± SEM depicted). [score:3]
To determine the tissue specific expression pattern of miR-196a, quantitative real-time PCR was performed. [score:3]
Mature miRNA-196a mimic (MIMAT0000226) and negative control cel-miR-67 (CN-001000-01-05) were obtained from Dharmacon Technologies (Dharmacon Inc, Lafayette, CO), and diluted with RNase free water to a final concentration of 10 μM and 20 μM before microinjection (The final concentration used for microinjection was 20 μM based on initial experiments showing this concentration is more effective in repressing Nobox expression). [score:3]
The efficiency of NOBOX mRNA/protein knockdown in miRNA-196a mimic injected and control embryos was determined by quantitative real-time PCR analysis and immunocytochemistry in eight-cell stage embryos as described previously [30]. [score:2]
Collectively, our results demonstrate that miR-196a is a bona fide negative regulator of NOBOX during bovine early embryogenesis. [score:2]
Luciferase activity was restored when a four-base mismatch mutation was introduced into the seed region of the miRNA-196a recognition sequence in the NOBOX 3' UTR (Figure 4B). [score:2]
Mutations in the predicted MRE in the 3' UTR of the NOBOX for miR-196a were created such that interaction between miR-196a and NOBOX is compromised (Figure 4A). [score:2]
These data indicate the predicted MRE is critical for the direct and specific binding of miR-196a to NOBOX transcript. [score:2]
Future studies of interest will investigate whether loss of miR-196a has any effect on the early embryonic development and identify putative miR-196a targets by next generation sequencing analysis of miR-196a depleted and wild type embryos. [score:2]
To confirm the binding of miR-196a to bovine NOBOX in vitro, HeLa cell transfection studies were conducted. [score:1]
miR-196a is an evolutionary conserved miRNA that has been identified in a wide range of vertebrate species. [score:1]
RNA secondary structure prediction analysis using Mfold [34] revealed that the apparent miR-196a binding site was positioned on a hairpin-loop structure, in an exposed position, which might facilitate miRNA accessibility. [score:1]
Figure 1 Prediction of a miR-196a binding site in the 3' UTR of bovine NOBOX mRNA. [score:1]
miR-196a binds to the 3' UTR of bovine NOBOX. [score:1]
miR-196a was chosen for further studies, because the predicted MRE in the bovine NOBOX 3' UTR had a low predicted free energy of hybridization with the cognate miRNA (-19.8 kcal/mol), suggesting a stable miRNA: mRNA duplex within the 9 nucleotide (nt) seed region at the 5' end of the miRNA (Figure 1). [score:1]
Repression of luciferase reporter gene activity by miR-196a was abolished when the MRE was mutated. [score:1]
The predicted miR-196a binding site is underlined. [score:1]
miR-196a represses endogenous NOBOX in bovine early embryos. [score:1]
Microinjection of miR-196a mimic in bovine embryos significantly reduced NOBOX mRNA levels in eight-cell embryos by more than 80% relative to uninjected and negative control miRNA -injected embryos (Figure 5B). [score:1]
Using an algorithm "MicroInspector", a potential microRNA recognition element (MRE) for miR-196a was identified in the 3' UTR of the bovine NOBOX mRNA. [score:1]
The lack of conservation of miR-196a recognition sequence in bovine NOBOX might be due to the rapid drifting of 3' UTR during evolution [31, 35]. [score:1]
Furthermore, luciferase reporter assays were performed to validate specificity of the miR-196a regulation of NOBOX through the predicted miR-196a recognition sequence in the 3' UTR of NOBOX. [score:1]
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2
[+] score: 30
A possible explanation for the presence of target gene/microRNA combinations within single transcription units and for the targeting of nearby Hox genes by both miR-10 and miR-196, may lie in the complexity of the Hox regulatory mechanisms which involve multiple global and local transcriptional elements. [score:6]
The short genomic distances between miR-196 and miR-10 and their targets are remarkable; miR-10c is ∼25 kb from the target sites in HoxB3a and ∼48 kb from those in HoxB1a and (in mammals) a miR-196 paralogue is located at ∼18 kb from HoxB8 and HoxC8 and at ∼14 kb from HoxA7. [score:5]
With respect to the Hox related microRNAs, HoxA7 and Hox-8 paralogues have been identified as targets of miR-196 [23], [24], [25]. [score:3]
MiR-196 is known to represses HoxB8, HoxC8, HoxD8 and HoxA7 and we have identified HoxB1a and HoxB3a as targets for miR-10. [score:3]
C) Polycistronic transcripts identified from the EST database show inclusion of miR-196 paralogues and HoxB8 and HoxC8 target genes on the same primary transcripts. [score:3]
As with the previously described interactions between miR-196 and HoxA7 and Hox-8 paralogues, the target genes are located in close proximity to the microRNA. [score:3]
In Drosophila, a conserved or possibly convergent interaction exists for the miR-196 homologue IAB-4 which targets the Ubx Hox gene [26]. [score:3]
In addition to the Hox coding genes, the miR-10, miR-196 and miR-615 microRNA gene families have been identified within the vertebrate Hox clusters [8]– [11]. [score:1]
In the Hox clusters, miR-10 genes are closely associated with the positions of Hox-4 paralogue members, miR-196 is located 5′ of Hox-9 paralogues and the more recently cloned miR-615 is located in the HoxC5 intron in mammals but appears to be absent from Teleosts and Xenopus tropicalis. [score:1]
Similar transcripts are present in the EST database for miR-196a-1/ HoxB8 and miR-196a-2/ HoxC8 (figure 9C). [score:1]
In addition to the protein coding Hox genes, the miR-10, miR-196 and miR-615 families of microRNA genes are conserved within the vertebrate Hox clusters. [score:1]
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3
[+] score: 12
To exemplify how lncRNAs could participate in the miRNA-mRNA interaction network, we have considered an example of hsa-mir-196a, which is experimentally known to target ENST0000040584, ENST00000242159, ENST00000313173 mRNA transcripts, encoded by the HOX cluster genes HOXC8, HOXA7 and HOXD8 [49], We noticed that the hsa-mir-196a could also target lncRNAs ENST00000519935, ENST00000523790, and ENST00000489695 (Figure 4B2). [score:4]
The mir-196 miRNAs are known to directly cleave HOX mRNAs and modulates development of axial patterning [49], [50]. [score:3]
Thus lncRNAs could potentially modulate the pathogenesis of the disease by modulating the key partner, mir-196a. [score:3]
The human miRNA hsa-mir-196a has been previously shown to be associated with the pathogenesis of cancers including colorectal cancer cells and has been shown to induce a pro-oncogenic behavior in human cancer cells [51]. [score:1]
B1: An interesting example from the network highlighted in orange showing interactions between of network highlighting miRNA: (a) hsa-mir-9; lncRNA: (d) ENST00000500197.2, (e) ENST00000509783.1, (f) ENST00000511014.1, (h) ENST00000505030.1, (i) ENST00000504246.1; mRNA: (b) ENST00000384838.1, (c) ENST00000262095.2, (g) ENST00000491143.1, (j) ENST00000226574 B2: Another interesting example from the network highlighted in blue showing interactions between miRNA: (1) hsa-miR-196a, (5) hsa-miR-196b*, (13)hsa- miR-196b; lncRNA: (4) ENST00000523790.1; (6) ENST00000489695.1, (12) ENST00000519935.1; mRNA: (2) ENST00000354032.4, (3) ENST00000384852.1, (7) ENST00000313173, (8) ENST0000024215, (9) ENST00000040584, (10) ENST00000304786.7, (11) ENST00000366839.4. [score:1]
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4
[+] score: 11
The three families we identified, miR-10, miR-99/100 and miR-196, are highly conserved and are dysregulated in a number of human diseases. [score:4]
The miR-10, miR-99/100 and miR-196 families are some of the most common Hox gene -targeting miRNAs yet described. [score:3]
One notable example is the ability for miR-196a to bind a perfectly complementary 22nt sequence in the 3′UTR of HoxB8, a rare case in mammals that causes cleavage of the transcript similar to the activity of an siRNA (38, 39). [score:1]
The authors also found that miR-99a and miR-196a are stabilized by GLD2 despite lacking a 3′ GLD2 stabilizing sequence (9). [score:1]
Also worth noting is the similarity in the seed sequence between let-7 family miRNAs and miR-196a/b. [score:1]
The predicted miRNAs found in our search comprise four families, specifically: let-7, miR-99/100, miR-196a/b and miR-10a/b family members. [score:1]
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5
[+] score: 7
One of the teleost specific cliques contains mir196-Aa [see Additional File 1]. [score:1]
The CNSs were mainly teleost and neoteleost-specific, and we could identify two microRNAs in all species: mir196-Ca and mir10-Ca [see Additional File 5]. [score:1]
The footprint clique containing mir196-Ab did not identify a orthologous sequence for medaka, suggesting a lineage-specific loss of this microRNA in medaka [see Additional File 2]. [score:1]
The analyses revealed the existence of mir196-Ba in all teleosts – except for medaka – and mir10-Ba was found in all species but A. burtoni, due to missing sequence data [see Additional File 3]. [score:1]
In contrast to a previous study, we were able to identify mir196-Ab and mir196-Ba in the zebrafish clusters [86], probably due to increased sequence quality of the genomic sequence. [score:1]
An equivalent to the mir196-Cb could not be identified in neoteleosts, which have lost the entire HoxCb cluster. [score:1]
In medaka, we were not able to identify mir196-Ab, mir196-Ba and mir10-Bb, even though sequences were complete and without gaps in these intergenic regions. [score:1]
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6
[+] score: 4
The mir-196 family regulates Hox8 and Hox7 genes, the function of mir10 is unknown. [score:2]
The mir10 and the mir196 precursors are located at specific positions in the Hox gene clusters [4- 7]. [score:1]
A few microRNAs are apparently linked to protein coding genes, most notably mir-10 and mir-196 which are located in the (short) intergenic regions in the Hox gene clusters of vertebrates [4- 7]. [score:1]
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7
[+] score: 2
Recently we demonstrated that miR-196a and miR-181a function as negative regulators for two key oocyte-specific maternal effect genes (NOBOX and NPM2) essential for early embryogenesis [33] [29]. [score:2]
[1 to 20 of 1 sentences]
8
[+] score: 1
Other miRNAs from this paper: dre-mir-196a-1, dre-mir-199-1, dre-mir-199-2, dre-mir-199-3, dre-mir-203a, dre-mir-210, dre-mir-214, dre-mir-219-1, dre-mir-219-2, dre-mir-221, dre-mir-222a, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, dre-mir-429a, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-1-2, dre-mir-1-1, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-21-1, dre-mir-21-2, dre-mir-25, dre-mir-30e-2, dre-mir-101a, dre-mir-103, dre-mir-107a, dre-mir-122, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-126a, dre-mir-129-2, dre-mir-129-1, dre-mir-130b, dre-mir-130c-1, dre-mir-130c-2, dre-mir-133a-2, dre-mir-133a-1, dre-mir-133b, dre-mir-133c, dre-mir-135c-1, dre-mir-135c-2, dre-mir-140, dre-mir-142a, dre-mir-142b, dre-mir-150, dre-mir-152, dre-mir-462, dre-mir-196b, dre-mir-202, dre-mir-203b, dre-mir-219-3, dre-mir-365-1, dre-mir-365-2, dre-mir-365-3, dre-mir-455-1, dre-mir-430c-2, dre-mir-430c-3, dre-mir-430c-4, dre-mir-430c-5, dre-mir-430c-6, dre-mir-430c-7, dre-mir-430c-8, dre-mir-430c-9, dre-mir-430c-10, dre-mir-430c-11, dre-mir-430c-12, dre-mir-430c-13, dre-mir-430c-14, dre-mir-430c-15, dre-mir-430c-16, dre-mir-430c-17, dre-mir-430c-18, dre-mir-430a-2, dre-mir-430a-3, dre-mir-430a-4, dre-mir-430a-5, dre-mir-430a-6, dre-mir-430a-7, dre-mir-430a-8, dre-mir-430a-9, dre-mir-430a-10, dre-mir-430a-11, dre-mir-430a-12, dre-mir-430a-13, dre-mir-430a-14, dre-mir-430a-15, dre-mir-430a-16, dre-mir-430a-17, dre-mir-430a-18, dre-mir-430i-1, dre-mir-430i-2, dre-mir-430i-3, dre-mir-430b-2, dre-mir-430b-3, dre-mir-430b-4, dre-mir-430b-6, dre-mir-430b-7, dre-mir-430b-8, dre-mir-430b-9, dre-mir-430b-10, dre-mir-430b-11, dre-mir-430b-12, dre-mir-430b-13, dre-mir-430b-14, dre-mir-430b-15, dre-mir-430b-16, dre-mir-430b-17, dre-mir-430b-18, dre-mir-430b-5, dre-mir-430b-19, dre-mir-430b-20, dre-let-7j, dre-mir-135b, dre-mir-135a, dre-mir-499, dre-mir-738, dre-mir-429b, dre-mir-1788, dre-mir-196c, dre-mir-107b, dre-mir-455-2, dre-mir-222b, dre-mir-126b, dre-mir-196d, dre-mir-129-3, dre-mir-129-4
Interestingly, the conserved novel miRNAs retrieved by miRDeep, namely miR_4 (miR-429 family), miR_5 (miR-429 family), miR_6 (miR-1788 family), miR_11 (miR-196 family), miR_15 (miR-196 family), miR_16 (miR-103 family) and miR_21 (miR-222 family) were also predicted as novel ZF miRNAs by Ensembl algorithms (Table 4). [score:1]
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9
[+] score: 1
The role of microRNAs in lower vertebrates with a known regenerative ability is gaining a lot of attention, with several recent studies identifying miRNAs associated with spinal cord repair (e. g., miR-125b in axolotl, miR-133b in zebrafish; [28, 29]) and appendage regeneration (e. g. miR-196 in axolotl tail, miR-203 in zebrafish fin; [30, 31]). [score:1]
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