Temperature-dependent gene expression in hyperthermia

Abstract

[Background]

We have reported that “temperature” is a factor that controls global gene expression profiles. In RNA silencing, microRNA (miRNA), a small non-coding RNA, inhibits gene expression in temperature-dependent mechanism. In this study, we aimed to clarify the molecular basis of gene expression machinery, which may affect pathogenesis, depending on temperature.

[Methods]

In this study, we analyzed the regulatory mechanism of temperature-dependent gene expression mechanism using molecular biology and cell biology combined with bioinformatics.

[Results]

Gene repression efficiencies via RNA silencing by miRNAs were examined using cultured cells derived from Drosophila or human at different growth temperatures. As a result, it was revealed that the microRNA shows temperature-dependent repression effect on target gene expression. Such results are consistent with our previous result that RNA silencing efficiency by a miRNA is regulated by the thermodynamic property in base-pairing between a miRNA and target mRNAs. Furthermore, it was found that almost all of the target genes of a miRNA were changed by A-to-I type of chemical modification in the miRNA, and the gene suppression efficiency of the modified miRNA was strictly controlled by the changes of thermodynamic properties due to the chemical modification. Furthermore, it was revealed that the functional RNA strand within miRNA duplex is often converted by the chemical modification, since thermodynamic stability of base-pairing is also responsible for unwinding of miRNA duplex.

[Conclusion]

It was revealed that the molecular mechanism by which the pattern of gene expression by miRNA was changed depending on body temperature or growth temperature. Thus, the hyperthermia therapy should be one of the possible strategies for regulating gene expression patterns by miRNA. Based on this research, it is expected to elucidate the causes and treatments of diseases by miRNAs depending on temperature.