What are miRNAs?
MicroRNAs (miRNAs) are the natural equivalents of siRNAs. Like siRNAs, miRNAs are approximately 21 nucleotides long and affect gene expression by interacting with messenger RNAs. Unlike siRNAs, miRNAs are encoded in the human genome and are used as a natural regulator of global gene expression. More than 500 miRNAs are encoded in the human genome and are expressed and processed by a combination of proteins in the nucleus and cytoplasm. miRNAs are highly conserved among vertebrates and comprise approximately 2% of all mammalian genes. miRNAs act as natural antisense molecules that negatively regulate the expression of genes with sequences that are complementary to the miRNAs (Figure 1). Since each miRNA appears to regulate the expression of tens to hundreds of different genes, miRNAs can function as “master-switches”, efficiently regulating and coordinating multiple cellular pathways and processes. By coordinating the expression of multiple genes, miRNAs play key roles in embryonic development, immunity, inflammation, as well as cellular growth and proliferation.
Figure 1: Current model of the microRNA mechanism
The growing awareness of the importance of miRNAs has generated intense activity in the biomedical research community. The first published report of a miRNA occurred in 1993 and resulted from a genetic screen in worms. The worm miRNA was the only known small RNA until 1999, when a second miRNA was discovered. The miRNAs appeared to be an oddity of worms until 2001, when the cloning and sequencing of more than 100 human and mouse miRNAs was described in a publication in Science (Lagos-Quintana et al., Science, 2001). Since then there has been an explosion in the number of publications related to miRNAs, with a substantial number of those describing the contributions of various miRNAs to cancer development (Figure 2).
Figure 2: Peer-reviewed microRNA publications