Elsevier, European Journal of Cancer, 10(43), p. 1529-1544
MicroRNAs are a recently discovered class of small, evolutionarily conserved, RNA molecules that negatively regulate gene expression at the post-transcriptional level. Mature microRNAs of approximately 20-22 nucleotides are formed from longer primary transcripts by two sequential processing steps mediated by a nuclear (Drosha) and a cytoplasmic (Dicer) RNAse III endonuclease. In the context of a protein complex, the RNA-induced silencing complex (RISC), microRNAs base-pair with target messenger RNA sequences causing translational repression and/or messenger RNA degradation. MicroRNAs have been implicated in the control of many fundamental cellular and physiological processes such as tissue development, cellular differentiation and proliferation, metabolic and signalling pathways, apoptosis and stem cell maintenance. Mounting evidence indicates that microRNAs also play a significant role in cellular transformation and carcinogenesis acting either as oncogenes or tumour suppressors. This review briefly introduces microRNAs in a historical perspective and focuses on the biogenesis of microRNAs, their mode of action, mammalian microRNA functions with emphasis on their involvement in disease - particularly cancer - and their potential therapeutic use.