MicroRNAs: components of an integrated system controlling cardiac development, physiology, and disease pathogenesis

See reviews in this series by Fazi and Nervi,21 Thum et al. ,22 Yang et al. ,23 and Urbich et al. 24 Protein-encoding sequences comprise <1.5% of the human genome.1 Nevertheless, a considerable fraction (∼90%) of the genome is effectively transcribed.2 Therefore, most of the transcriptional output of the genome of higher organisms seems to consist of non-coding (nc) RNAs, i.e. RNA that is not translated into a protein end product.3 It is now clear that much of this genomic output is not just transcriptional background noise of ‘junk’ DNA but an intricate RNA-based network constituting a level of regulation that appears as important as posttranscriptional protein modification. Only a limited number of ncRNA species predominantly maintaining basic biochemical processes, such as ribosomal RNA and transfer RNA, have been analysed in depth, but other types of ncRNAs have now been identified and are being studied.4 These ncRNAs regulate the gene expression process at many of its steps, from the epigenetic level down to translation, through a variety of mechanisms ( Figure 1 ).5 ncRNA has also been implicated in surprising areas, such as the integrity of cellular structure,6 and many other fascinating functions probably await discovery.Figure 1 Outline of some ncRNA functions. The central dogma of the flow …