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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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High rates of coexpression of intragenic miRNAs with host genes in the breast cancer and prostate cancer sample sets are, at least in part, related to the predominance of ‘conserved’ intragenic miRNAs. (A) Proportions of ‘conserved’ and ‘non-conserved’ intragenic miRNAs in the five sample sets. (B) Proportion of intragenic miRNAs that coexpressed with their host genes when using intragenic miRNAs from the breast cancer set and prostate cancer sample set, respectively. Based on raw P-values.
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gkr1312-F3: High rates of coexpression of intragenic miRNAs with host genes in the breast cancer and prostate cancer sample sets are, at least in part, related to the predominance of ‘conserved’ intragenic miRNAs. (A) Proportions of ‘conserved’ and ‘non-conserved’ intragenic miRNAs in the five sample sets. (B) Proportion of intragenic miRNAs that coexpressed with their host genes when using intragenic miRNAs from the breast cancer set and prostate cancer sample set, respectively. Based on raw P-values.

Mentions: The higher coexpression rate in breast cancer or prostate sample set (60%) than in other three data sets (16–24%) is likely related with a higher proportion of conserved intragenic miRNAs (Figure 3A). If only considering miRNAs in breast cancer or prostate cancer sample set, the coexpression rate was also increased in the other three sample sets compared to that of entire miRNA set (Figure 3B).Figure 3.


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)

High rates of coexpression of intragenic miRNAs with host genes in the breast cancer and prostate cancer sample sets are, at least in part, related to the predominance of ‘conserved’ intragenic miRNAs. (A) Proportions of ‘conserved’ and ‘non-conserved’ intragenic miRNAs in the five sample sets. (B) Proportion of intragenic miRNAs that coexpressed with their host genes when using intragenic miRNAs from the breast cancer set and prostate cancer sample set, respectively. Based on raw P-values.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkr1312-F3: High rates of coexpression of intragenic miRNAs with host genes in the breast cancer and prostate cancer sample sets are, at least in part, related to the predominance of ‘conserved’ intragenic miRNAs. (A) Proportions of ‘conserved’ and ‘non-conserved’ intragenic miRNAs in the five sample sets. (B) Proportion of intragenic miRNAs that coexpressed with their host genes when using intragenic miRNAs from the breast cancer set and prostate cancer sample set, respectively. Based on raw P-values.
Mentions: The higher coexpression rate in breast cancer or prostate sample set (60%) than in other three data sets (16–24%) is likely related with a higher proportion of conserved intragenic miRNAs (Figure 3A). If only considering miRNAs in breast cancer or prostate cancer sample set, the coexpression rate was also increased in the other three sample sets compared to that of entire miRNA set (Figure 3B).Figure 3.

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
Related in: MedlinePlus