Circulating microRNAs as biomarkers: A new frontier in diagnostics

✍ Scribed by Clifford J. Steer; Subbaya Subramanian

• Book ID: 102933682
• Publisher: John Wiley and Sons
• Year: 2012
• Tongue: English
• Weight: 873 KB
• Volume: 18
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.23377

✦ Synopsis

Mature microRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs that are initially transcribed as primary transcripts [primary microRNAs (pri-miRNAs)]. 1 miRNAs have been identified in a wide range of species, and approximately 1400 are found in humans. It has been estimated that more than 60% of human protein-coding genes are regulated by miRNAs, which thus potentially contribute to health and disease. 2 The majority of pri-miRNAs are located in either introns or exons of protein-coding genes, and the remainder are transcribed from intergenic regions. These pri-miRNAs are reduced in size by the ribonuclease III enzyme Drosha to approximately 70-nucleotide-long stem-loop precursors called precursor microRNAs (pre-miRNAs). These structures are exported into the cytoplasm by exportin 5 and then are processed by Dicer, an endonuclease, to form mature duplex miRNAs; these are then incorporated into an RNA-induced silencing complex (RISC) in which the passenger strand is selectively degraded. Along with Argonaute 2 and other RISC factors, the mature, approximately 20-to 22-nucleotide-long miR-NAs bind to complementary sites on messenger RNA transcripts to induce either translational pausing or, more commonly, transcript degradation. 3 The balancing and maintenance of the threshold levels of these miRNAs constitute a highly complex system uniquely designed for the delicate control of gene regulation.