One of the most important achievements in the post-genome era is discovery of microRNAs (miRNAs), which widely exist from simple-genome organisms such as viruses and bacteria to complex-genome organisms such as plants and animals. miRNAs are single-stranded non-coding RNAs of 18–25 nucleotides in length, which are generated from larger precursors that are transcribed from non-coding genes. As a new type of regulatory molecules, miRNAs present unique features in regulating gene and its products, including rapidly turning off protein production, reversibly, and compartmentalized regulating gene expression. These features must allow miRNAs to quickly respond to subtle environmental changes or intracellular stresses. The collection of five review articles in this issue aims to address how these small molecules play their regulatory roles in various physiological or pathological processes.
In the first review article, Drs Hu and Gatti discuss how DNA damage, particularly DNA double-strand break damage, regulates miRNA transcription as well as modulates miRNA processing and maturation. They conclude that DNA damage can induce the transcription of specific miRNAs and/or influence the expression of a subset of miRNA by modulating miRNA processing. In addition, the authors also describe a new role for miRNAs in regulating the cellular response to DNA double-strand break damage and the implications of the miRNA's role in DNA double-strand break to stem cells.
Before the discovery of miRNAs, transcriptional factors are thought to be major gene-modulators. So, it must be an interesting question what is the regulatory relationship between miRNAs and transcriptional factors. In the second review article, Dr Li and colleagues try to answer this question based on the interactions between nuclear factor κB (NF-κB) and related miRNAs. They select five particular miRNAs that highly involve in the NF-κB signaling for detailed discussion. In addition, they also describe a regulating network between NF-κB pathway and miRNAs, and discuss dysregulation of miRNAs and NF-κB in cancer.
It is well known that animal can control their physiological activities through lowering its metabolic rate that is below the standard resting rate. In their review article, Drs Storey and Biggar draw a new miRNA link to the molecular mechanisms of metabolic rate depression. The authors focus on researches with three animal models in mechanisms of hypometabolism and the inducible specific miRNA expressions responding to environmental stress.
miRNAs not only involve in regulating normal physiological activities described earlier, but also participate in controlling pathological progresses of various diseases such as cancer and neurodegenerative disorders. Drs Pertsemlidis and Du discuss the roles of miRNA regulation on these two seemingly dichotomous diseases. They conclude that miRNAs may play in the regulation of both the disparate and common pathways involved in the pathogenesis of neurodegenerative disease and malignant growth, and converge in the dysregulation of gene expression at the post-transcriptional level.
In the last review article of this collection, Dr Witzany tries to ask a theoretical question how to edit natural genomes. According to his opinion, trans-editing agents must be required in order to modify nucleotide sequences of DNA-coding genetic information of proteins at genomic and transcriptional levels, and these editing agents mainly include viral agents, transposable elements and no-coding RNAs. Therefore, Dr Witzany's essay might provide a logical explanation for existence of miRNAs in natural genomes.
In these review articles, various physiological or pathological roles and regulating mechanisms of miRNAs have been informatively described and discussed, which must be helpful for further studying and understanding miRNA behaviors in the near future.