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Young intragenic miRNAs are less coexpressed with host genes than old ones: implications of miRNA-host gene coevolution.

He C, Li Z, Chen P, Huang H, Hurst LD, Chen J - Nucleic Acids Res. (2012)

Bottom Line: This result is robust: in all sample sets, the coexpression rate of young miRNAs is significantly lower than that of conserved ones even after controlling for abundance.As a result, although young miRNAs dominate in human genome, the majority of intragenic miRNAs that show coexpression with host genes are phylogenetically old ones.We propose a model to explain this phenomenon in which the majority of young miRNAs are unlikely to be coexpressed with host genes; however, for some fraction of young miRNAs coexpression with their host genes, initially imbued by chromatin level effects, is advantageous and these are the ones likely to embed into the system and evolve ever higher levels of coexpression, possibly by evolving piggybacking mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

ABSTRACT
MicroRNAs (miRNAs) have emerged as key regulators of gene expression. Intragenic miRNAs account for ∼50% of mammalian miRNAs. Classic studies reported that they are usually coexpressed with host genes. Here, using genome-wide miRNA and gene expression profiles from five sample sets, we show that evolutionarily conserved ('old') intragenic miRNAs tend to be coexpressed with host genes, but non-conserved ('young') ones rarely do so. This result is robust: in all sample sets, the coexpression rate of young miRNAs is significantly lower than that of conserved ones even after controlling for abundance. As a result, although young miRNAs dominate in human genome, the majority of intragenic miRNAs that show coexpression with host genes are phylogenetically old ones. For younger miRNAs, extrapolation of their expression profiles from those of their host genes should be treated with caution. We propose a model to explain this phenomenon in which the majority of young miRNAs are unlikely to be coexpressed with host genes; however, for some fraction of young miRNAs coexpression with their host genes, initially imbued by chromatin level effects, is advantageous and these are the ones likely to embed into the system and evolve ever higher levels of coexpression, possibly by evolving piggybacking mechanisms.

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Proportion of intragenic miRNAs that are likely coexpressed with their host genes in each individual sample set and the average proportions across the five sample sets. Based on the raw P-values.
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gkr1312-F1: Proportion of intragenic miRNAs that are likely coexpressed with their host genes in each individual sample set and the average proportions across the five sample sets. Based on the raw P-values.

Mentions: Although the rate of potential coexpression between intragenic miRNAs and host genes varies greatly between different data sets (e.g. only 16–24% in the human leukemia, myeloma or lymphoblastoid cell samples, but as high as 60% in both human breast cancer and prostate samples; Pearson correlation; based on raw P-values), we observed that conserved intragenic miRNAs exhibited a significantly (P < 0.01, chi-square test) higher rate of coexpression with their host genes than non-conserved ones in each data set (Table 2 and Figure 1; all the intragenic miRNAs with reliable expression values in each data set have conservation information from TargetScan). On average, 53% (based on raw P-values) or 30% (Bonferroni correction) of ‘conserved’, whereas only 19% (based on raw P-values) or 10% (Bonferroni correction) of ‘non-conserved’ intragenic miRNAs are likely coexpressed with their host genes across the five sample sets (P < 0.05, Wilcoxon rank test—based on either raw or adjusted P-values; Figure 1 and Table 2). The difference of coexpression rate between ‘conserved’ and ‘non-conserved’ subgroups was also significant (P < 0.05, Wilcoxon rank test) in both intronic and exonic miRNAs (Table 2).Figure 1.


Young intragenic miRNAs are less coexpressed with host genes than old ones: implications of miRNA-host gene coevolution.

He C, Li Z, Chen P, Huang H, Hurst LD, Chen J - Nucleic Acids Res. (2012)

Proportion of intragenic miRNAs that are likely coexpressed with their host genes in each individual sample set and the average proportions across the five sample sets. Based on the raw P-values.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351155&req=5

gkr1312-F1: Proportion of intragenic miRNAs that are likely coexpressed with their host genes in each individual sample set and the average proportions across the five sample sets. Based on the raw P-values.
Mentions: Although the rate of potential coexpression between intragenic miRNAs and host genes varies greatly between different data sets (e.g. only 16–24% in the human leukemia, myeloma or lymphoblastoid cell samples, but as high as 60% in both human breast cancer and prostate samples; Pearson correlation; based on raw P-values), we observed that conserved intragenic miRNAs exhibited a significantly (P < 0.01, chi-square test) higher rate of coexpression with their host genes than non-conserved ones in each data set (Table 2 and Figure 1; all the intragenic miRNAs with reliable expression values in each data set have conservation information from TargetScan). On average, 53% (based on raw P-values) or 30% (Bonferroni correction) of ‘conserved’, whereas only 19% (based on raw P-values) or 10% (Bonferroni correction) of ‘non-conserved’ intragenic miRNAs are likely coexpressed with their host genes across the five sample sets (P < 0.05, Wilcoxon rank test—based on either raw or adjusted P-values; Figure 1 and Table 2). The difference of coexpression rate between ‘conserved’ and ‘non-conserved’ subgroups was also significant (P < 0.05, Wilcoxon rank test) in both intronic and exonic miRNAs (Table 2).Figure 1.

Bottom Line: This result is robust: in all sample sets, the coexpression rate of young miRNAs is significantly lower than that of conserved ones even after controlling for abundance.As a result, although young miRNAs dominate in human genome, the majority of intragenic miRNAs that show coexpression with host genes are phylogenetically old ones.We propose a model to explain this phenomenon in which the majority of young miRNAs are unlikely to be coexpressed with host genes; however, for some fraction of young miRNAs coexpression with their host genes, initially imbued by chromatin level effects, is advantageous and these are the ones likely to embed into the system and evolve ever higher levels of coexpression, possibly by evolving piggybacking mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

ABSTRACT
MicroRNAs (miRNAs) have emerged as key regulators of gene expression. Intragenic miRNAs account for ∼50% of mammalian miRNAs. Classic studies reported that they are usually coexpressed with host genes. Here, using genome-wide miRNA and gene expression profiles from five sample sets, we show that evolutionarily conserved ('old') intragenic miRNAs tend to be coexpressed with host genes, but non-conserved ('young') ones rarely do so. This result is robust: in all sample sets, the coexpression rate of young miRNAs is significantly lower than that of conserved ones even after controlling for abundance. As a result, although young miRNAs dominate in human genome, the majority of intragenic miRNAs that show coexpression with host genes are phylogenetically old ones. For younger miRNAs, extrapolation of their expression profiles from those of their host genes should be treated with caution. We propose a model to explain this phenomenon in which the majority of young miRNAs are unlikely to be coexpressed with host genes; however, for some fraction of young miRNAs coexpression with their host genes, initially imbued by chromatin level effects, is advantageous and these are the ones likely to embed into the system and evolve ever higher levels of coexpression, possibly by evolving piggybacking mechanisms.

Show MeSH