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Effects of genetic variations on microRNA: target interactions.

Liu C, Rennie WA, Carmack CS, Kanoria S, Cheng J, Lu J, Ding Y - Nucleic Acids Res. (2014)

Bottom Line: We perform a transcriptome-scale analysis of genetic variants and miRNA:target interactions identified by CLASH.Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA:target hybridization but also the structural accessibility of the binding sites and flanking regions.Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.

View Article: PubMed Central - PubMed

Affiliation: Wadsworth Center, New York State Department of Health, Center for Medical Science, 150 New Scotland Avenue, Albany, NY 12208, USA.

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Variant densities in whole transcriptome, CLASH transcripts and miRNA binding sites for (A) common variants (MAF ≥ 1%); (B) rare variants (MAF <1%); (C) percentages of miRNA binding sites by evolutionary conservation levels; (D) density of variants (common or rare) with different MAF thresholds for miRNA binding sites grouped by conservation level.
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Figure 1: Variant densities in whole transcriptome, CLASH transcripts and miRNA binding sites for (A) common variants (MAF ≥ 1%); (B) rare variants (MAF <1%); (C) percentages of miRNA binding sites by evolutionary conservation levels; (D) density of variants (common or rare) with different MAF thresholds for miRNA binding sites grouped by conservation level.

Mentions: We focus on presenting results using the common MAF thresholds of 1% defining common variants and rare variants. The conclusions are generalizable to a wide range of thresholds (Supplementary Figure S1). For both common and rare variants in the three target regions (mRNA, CDS and 3′ UTR), the densities for CLASH transcripts (blue bars in Figure 1A and B) are significantly lower than those for the whole transcriptome (red bars in Figure 1A and B), with all P-values under 0.04 for density comparisons. It indicates that miRNA binding sites are more likely to reside within those targets in the transcriptome with lower variant densities, consistent with a previous study (21). In all of the three target regions (mRNA, CDS and 3′ UTR), for common variants, the densities for miRNA binding site (green bars in Figure 1A) are significantly lower than those for the CLASH transcripts (blue bars in Figure 1A), with all P-values under 0.03. For rare variants, the densities for miRNA binding site (green bars in Figure 1B) are marginally higher than those for the CLASH transcripts (blue bars in Figure 1B). These suggest miRNAs binding sites are more likely to reside within target regions in which nucleotides have low mutation frequencies. Moreover, for common variants, the densities for 3′ UTRs are substantially higher than those of CDSs (Figure 1A); for rare variants, the densities for CDSs are substantially higher than those of the 3′ UTRs (Figure 1B). These indicate that rare variants tend to reside in CDSs, whereas common variants tend to reside in the 3′ UTRs. This may be due to the fact that under codon constraints, CDS tends to be more conserved than 3′ UTR.


Effects of genetic variations on microRNA: target interactions.

Liu C, Rennie WA, Carmack CS, Kanoria S, Cheng J, Lu J, Ding Y - Nucleic Acids Res. (2014)

Variant densities in whole transcriptome, CLASH transcripts and miRNA binding sites for (A) common variants (MAF ≥ 1%); (B) rare variants (MAF <1%); (C) percentages of miRNA binding sites by evolutionary conservation levels; (D) density of variants (common or rare) with different MAF thresholds for miRNA binding sites grouped by conservation level.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150780&req=5

Figure 1: Variant densities in whole transcriptome, CLASH transcripts and miRNA binding sites for (A) common variants (MAF ≥ 1%); (B) rare variants (MAF <1%); (C) percentages of miRNA binding sites by evolutionary conservation levels; (D) density of variants (common or rare) with different MAF thresholds for miRNA binding sites grouped by conservation level.
Mentions: We focus on presenting results using the common MAF thresholds of 1% defining common variants and rare variants. The conclusions are generalizable to a wide range of thresholds (Supplementary Figure S1). For both common and rare variants in the three target regions (mRNA, CDS and 3′ UTR), the densities for CLASH transcripts (blue bars in Figure 1A and B) are significantly lower than those for the whole transcriptome (red bars in Figure 1A and B), with all P-values under 0.04 for density comparisons. It indicates that miRNA binding sites are more likely to reside within those targets in the transcriptome with lower variant densities, consistent with a previous study (21). In all of the three target regions (mRNA, CDS and 3′ UTR), for common variants, the densities for miRNA binding site (green bars in Figure 1A) are significantly lower than those for the CLASH transcripts (blue bars in Figure 1A), with all P-values under 0.03. For rare variants, the densities for miRNA binding site (green bars in Figure 1B) are marginally higher than those for the CLASH transcripts (blue bars in Figure 1B). These suggest miRNAs binding sites are more likely to reside within target regions in which nucleotides have low mutation frequencies. Moreover, for common variants, the densities for 3′ UTRs are substantially higher than those of CDSs (Figure 1A); for rare variants, the densities for CDSs are substantially higher than those of the 3′ UTRs (Figure 1B). These indicate that rare variants tend to reside in CDSs, whereas common variants tend to reside in the 3′ UTRs. This may be due to the fact that under codon constraints, CDS tends to be more conserved than 3′ UTR.

Bottom Line: We perform a transcriptome-scale analysis of genetic variants and miRNA:target interactions identified by CLASH.Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA:target hybridization but also the structural accessibility of the binding sites and flanking regions.Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.

View Article: PubMed Central - PubMed

Affiliation: Wadsworth Center, New York State Department of Health, Center for Medical Science, 150 New Scotland Avenue, Albany, NY 12208, USA.

Show MeSH