Comparative Analysis of mi RNA ‐mediated Gene Regulation in Mammals

Abstract

Micro ribonucleic acids (miRNAs) are a class of small noncoding RNAs, which are involved in a range of physiological and pathological processes. All animal miRNAs share common genomic structure, biosynthetic pathways and reaction mechanisms but mammals seem to have more miRNAs to match their organism complexity and longer 3′‐UTR (untranslated region) to evaluate more miRNA target sites. During the episode of miRNA innovation observed at the vertebrates to the placental mammals, multiple unique miRNAs have emerged only in primates as compared with other mammals. The dramatically expanding of mammalian miRNAs and their targets suggest that miRNAs play important roles in mammalian evolution. Key concepts MicroRNAs (miRNAs) are group of small noncoding RNAs with approximately 22 nucleotides. miRNAs play important roles in many physiological and pathological processes in almost all eukaryotes, including development, cell proliferation, apoptosis, differentiation, tumours and many others. Compared with other animals, mammalians seem to have more miRNAs. The sequence of many miRNAs is conserved, like lin‐4 and let‐7 family, indicating strong functional constraint on miRNA evolution. However, nonconserved miRNAs represent a potentially important source of functional novelties during evolution. There is a rapid evolution of the miRNA cluster in primates, including frequent tandem duplications and nucleotide substitutions. All animal miRNAs share common genomic structure, biosynthetic pathways and reaction mechanisms. Each mammalian miRNA regulates on average 200 target genes whereas many genes have multiple target sites for either one miRNA or many different miRNAs. The avoidance of miRNA targeting might be as important as conservation of miRNA target sites in the evolution of tissue‐specific gene expression patterns. Some miRNAs are similarly expressed in mammals and most metazoans, indicating an evolutionarily conserved function, but others seem to be more ubiquitously expressed and only detected in specific cell types.

The roles of miRNAs as potential biomarkers in lung diseases

“…The first miRNA, named Lin-4, was identified in 1993(Lee et al, 1993 and miRNAs have subsequently been shown to be present in a wide variety of species from single-cell algae to humans. Phylogenetically, this class of molecule emerged before the diversification of unicellular to multicellular organisms and may, therefore, be envisaged as a primal, critical and necessary regulatory mechanism present throughout evolution (Zhang and Lv, 2001;Cai et al, 2009).…”

“…At the evolutionary level, the complexity of an organism correlates well with the number of miRNAs expressed. Mammals express the highest number of miRNAs (Zhang and Lv, 2001) with the human genome capable of expressing $ 1000 miR-NAs with tissue and cell specificity (O'Connell et al, 2012). miRNAs have the potential to target more than one hundred mRNAs and may therefore affect several biological pathways simultaneously (He and Hannon, 2004).…”