TY - JOUR
T1 - Young intragenic miRNAs are less coexpressed with host genes than old ones
T2 - Implications of miRNA-host gene coevolution
AU - He, Chunjiang
AU - Li, Zejuan
AU - Chen, Ping
AU - Huang, Hao
AU - Hurst, Laurence D.
AU - Chen, Jianjun
N1 - Funding Information:
G. Harold and Leila Y. Mathers Charitable Foundation (to J.C.); the National Institutes of Health (NIH) (R01 CA127277) (to J.C.); Gabrielle’s Angel Foundation (to J.C., Z.L. and H.H.) and Leukemia & Lymphoma Society Special Fellow (to Z.L.). LDH is a Royal Society Wolfson Research Merit Award Holder. Funding for open access charge: G. Harold and Leila Y. Mathers Charitable Foundation (to J.C.).
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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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U2 - 10.1093/nar/gkr1312
DO - 10.1093/nar/gkr1312
M3 - Article
C2 - 22238379
AN - SCOPUS:84861357388
SN - 0305-1048
VL - 40
SP - 4002
EP - 4012
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 9
ER -