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2 publications mentioning ptr-mir-299

Open access articles that are associated with the species Pan troglodytes and mention the gene name mir-299. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 51
To assess whether miRNA with expression divergence on the human lineage might be associated with human cognitive functions, we investigated the expression of genes targeted by five miRNA showing human-specific expression, according to multiple methodologies: miR-184, miR-487a, miR-383, miR-34c-5p and miR-299-3p (Figure 2). [score:7]
Potential influence of miRNA divergence on neuronal functions was further confirmed by preferential expression of the corresponding miR-299-3p and miR-184 in cortical neurons, as well as verification of the predicted miRNA-target relationship in two human neuroblastoma cell lines. [score:5]
While this substitution might affect relative stand selection efficiency during miRNA procession, as well as target selection, we did not find any significant differences in target effects between the human and the chimpanzee versions of miR-299-3p in our experiment (Figure S8). [score:5]
The X and Y-axis show the target effect produced by hsa-miR-299-3p and ptr-miR-299-3p transfection, respectively. [score:3]
To further test association of miR-184 and miR-299-3p with neuronal functions, we determined their expression patterns in the human and macaque prefrontal cortex by in situ hybridization with specific LNA-probes (Table S11). [score:3]
Similarly, targets of miR-299-3p were significantly enriched in the “axon guidance” pathway, which is associated with neuronal cell differentiation and functions. [score:3]
Similarly, based on the DIANA-mirPath algorithm [33], targets of miR-184, miR-487a and miR-299-3p were significantly enriched in KEGG pathways that are related to neural functions (Table S10). [score:3]
Requiring significant support by at least two out of three methodologies (sequencing, microarrays and Q-PCR), expression changes in five miRNA (miR-184, miR-299-3p, miR-487a, miR-383 and miR-34c-5p) could be assigned to the human evolutionary lineage and two (miR-375 and miR-154*) to the chimpanzee evolutionary lineage (Figure 2). [score:3]
We tested the effects of all five miRNA showing human-specific expression in brain, as well as effects of the chimpanzee version of miR-299-3p sequence. [score:3]
Further, in both cell lines we observed highly correlated target effects after transfection with human and chimpanzee versions of miR-299-3p. [score:3]
Figure S8 Target effects of human and chimpanzee variants of miRNA 299-3p (hsa-miR-299-3p and ptr-miR-299-3p) after transfection in two cell lines. [score:3]
Based on the DIANA-mirPath algorithm, targets of miR-184, miR-487a and miR-299-3p were significantly enriched in KEGG pathways that are related to neural functions (Table S10). [score:3]
The red legend in the bottom right corner of each plot shows the Pearson correlation coefficient of target effect between hsa-miR-299-3p transfection and ptr-miR-299-3p transfection into SH-SY5Y (panel A) and SK-N-SH (panel B) cell lines, calculated using Mock 1 as a negative control (R) and the correlation p-value (p). [score:1]
1002327.g004 Figure 4 In situ staining of miR-184 and miR-299-3p in prefrontal cortex. [score:1]
In situ staining of miR-184 and miR-299-3p in prefrontal cortex. [score:1]
On the DNA sequence level, these miRNA tend to be conserved: miR-184 mature miRNA sequence is evolutionarily conserved from insects to humans, with only one nucleotide different at 3′end of mature sequence, while miR-383 and miR-34c-5p are classified as broadly conserved and miR-299-3p - as conserved among animal species [25], [31]. [score:1]
We designed two LNA-probes complementary to miR-184 and miR-299-3p respectively (Table S11). [score:1]
We chose three types of miRNA differences: (1) consistent by both methodologies: miR-383 and miR-34c-5p; (2) significant according to sequencing, but unconfirmed in the microarray experiment: miR-143 and miR-499; (3) significant according to sequencing, but not detected or masked on the microarrays: miR-184 and miR-299-3p. [score:1]
The mature sequence of miR-299-3p contains human-specific C to T substitution at position 10. [score:1]
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2
[+] score: 48
Interestingly, MFE differences between the human and non-human hairpins of mir-299, mir-508 and mir-541 were in accordance with the differential expression levels observed between variants: more expressed variants showed higher stabilities and pairs of miRNA variants with stronger expression differences showed larger MFE differences. [score:7]
Specifically, the non-human versions of miR-299-3p and miR-541-3p were four and one and a half times more expressed than the human miRNAs respectively, whereas human miR-508-3p was seven times more expressed than the non-human version. [score:5]
Moreover, genes deregulated by miR-299-3p and miR-541-3p were involved in reproductive and infectious diseases and non-human miR-503-3p, human miR-508-3p and both variants of miR-541-3p were associated with neurological disorders. [score:4]
We found expression of miR-299-3p in brain, placenta and testis in all the studied primates and mouse. [score:3]
Remarkably, non-human miR-299-3p regulated genes with important roles in nervous system development and function. [score:3]
We next centered our interest in the analysis of the expression of four miRNAs with human-specific substitutions located either in the mature (miR-299-3p, miR-508-3p and miR-541-3p) or in the seed regions (miR-503-3p). [score:3]
On one hand, miR-299-3p and miR-541-3p change the expression of a large number of genes (between one and two thousands genes). [score:3]
In accordance we observed a significant expression of miR-299-3p and miR-541-3p in brain tissues from different primates. [score:3]
Remarkably, miR-299-3p was highly amplified in cerebellum but poorly detected in other brain regions whereas miR-508-3p and miR-541-3p were expressed in several regions such as hypothalamus, hippocampus, frontal, parietal and temporal cortex. [score:3]
The human and non-human versions of miR-299-3p and miR-541-3p deregulated more than one thousand genes, while both versions of miR-503-3p and miR-508-3p deregulated less than 300 genes. [score:3]
Human miR-299-3p and miR-541-3p deregulated about the 10% of the genes in an exclusive manner, but these proportions reached about 50% for human miR-503-3p and miR-508-3p. [score:2]
For expression level analyses, pre-miRNA genomic sequences of the selected miRNAs (mir-299, mir-503, mir-508 and mir-541) and ~100 bp flanking regions at each side were PCR amplified (primers in S2 Table). [score:2]
We have thoroughly studied the possible functional consequences of human-specific substitutions in the mature region of four miRNAs and show that miR-299-3p and miR-541-3p are conserved miRNAs with neuronal functions and thus evolutionary changes in these miRNAs may have had an impact in gene regulatory networks ultimately related to the evolution of the nervous system. [score:2]
We suggest that this could be the case for mir-299 and mir-508 for which the hairpin length between humans and the other great apes has been described to be different. [score:1]
For transcriptome analyses SH-SY5Y cells were transfected with 100 μM of miRNA mimic variants (miR-299-3p, miR-503-3p, miR-508-3p, miR-541-3p or the related negative control) as previously described [38]. [score:1]
After discarding polymorphism changes (1000 Genomes database) [34], four miRNA candidates were studied: miR-503-3p, with a single human-specific nucleotide substitution in the seed region, and miR-299-3p, miR-508-3p and miR-541-3p with human-specific nucleotide substitutions in the mature out of the seed region (Table 1). [score:1]
Besides nucleotide substitutions, precursor molecules of the human and non-human versions of mir-299 and mir-508 described in miRBase also differ in length (Fig 6). [score:1]
In addition, changes in the hairpin stabilities of mir-299 and mir-508 could also be affected by changes in the precursor molecule lengths. [score:1]
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