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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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Comparison of rates of coexpression with host genes between selected groups of conserved and non-conserved intragenic miRNAs that have similar expression abundance in each sample set (Table 3). Based on raw P-values.
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gkr1312-F4: Comparison of rates of coexpression with host genes between selected groups of conserved and non-conserved intragenic miRNAs that have similar expression abundance in each sample set (Table 3). Based on raw P-values.

Mentions: Notably, we still observed significantly (P < 0.01, chi-square test) higher coexpression rates between intragenic miRNAs and their host genes in ‘conserved’ than in ‘non-conserved’ ones in each sample set: 51% (27/53) of ‘conserved’ and 5% (3/61) of ‘non-conserved’ in leukemia sample set; 28% (20/72) of ‘conserved’ and 11% (4/35) of ‘non-conserved’ in myeloma sample set; 31% (13/42) of ‘conserved’ and 17% (15/88) of ‘non-conserved’ in lymphoblastoid cell line sample set; 80% (20/25) of ‘conserved’ and 36% (16/44) of ‘non-conserved’ in breast cancer sample set; 81% (17/21) of ‘conserved’ and 27% (7/26) of ‘non-conserved’ in prostate sample set, respectively (Table 3 and Figure 4). On average, 54% of the ‘conserved’ intragenic miRNAs are likely coexpressed with their host genes across the five sample sets, significantly (P < 0.05, Wilcoxon rank test) more frequent than the coexpression rate (19%) of ‘non-conserved’ ones.Figure 4.


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)

Comparison of rates of coexpression with host genes between selected groups of conserved and non-conserved intragenic miRNAs that have similar expression abundance in each sample set (Table 3). Based on raw P-values.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkr1312-F4: Comparison of rates of coexpression with host genes between selected groups of conserved and non-conserved intragenic miRNAs that have similar expression abundance in each sample set (Table 3). Based on raw P-values.
Mentions: Notably, we still observed significantly (P < 0.01, chi-square test) higher coexpression rates between intragenic miRNAs and their host genes in ‘conserved’ than in ‘non-conserved’ ones in each sample set: 51% (27/53) of ‘conserved’ and 5% (3/61) of ‘non-conserved’ in leukemia sample set; 28% (20/72) of ‘conserved’ and 11% (4/35) of ‘non-conserved’ in myeloma sample set; 31% (13/42) of ‘conserved’ and 17% (15/88) of ‘non-conserved’ in lymphoblastoid cell line sample set; 80% (20/25) of ‘conserved’ and 36% (16/44) of ‘non-conserved’ in breast cancer sample set; 81% (17/21) of ‘conserved’ and 27% (7/26) of ‘non-conserved’ in prostate sample set, respectively (Table 3 and Figure 4). On average, 54% of the ‘conserved’ intragenic miRNAs are likely coexpressed with their host genes across the five sample sets, significantly (P < 0.05, Wilcoxon rank test) more frequent than the coexpression rate (19%) of ‘non-conserved’ ones.Figure 4.

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