Noncoding RNAs

Recent years have witnessed many remarkable discoveries in the life sciences that have led to major paradigm shifts. An example is the emerging appreciation of the critical role of noncoding RNAs in a broad range of physiological and pathological processes. One such class of noncoding RNAs, the microRNAs (miRNAs), controls intricate networks of gene expression via post-transcriptional mechanisms. Originally described in animals by V. Ambros and G. Ruvkin in 1993, microRNAs are now recognized to impact human development and health in many ways. Another distinct and rapidly growing class of noncoding RNA, the long ncRNAs (lncRNAs), is also implicated in gene regulation and disease. Across the phylogenetic kingdoms, bacteria and other prokaryotes have proportionally the least amount of non-coding DNA. Interestingly the total number of protein-coding genes does not consistently increase with increasing complexity of organisms; for example, insects have just twice as many protein-coding genes (∼13,500) than yeast (∼6,000). Increasing cellularity also does not seem to affect the number of protein-coding genes in the genome. For example C. elegans, a worm that is well studied in developmental biology, has around 19,000 protein-coding genes that govern normal development and function of its 959 cells; whereas a similar number of protein coding genes (∼25,000) in humans drives development and function of over 10 trillion cells. One major difference between the worm and human genomes is the relative proportion of noncoding DNA, which is seen to increase with complexity of body plan and cellular processes. In recent years it has been demonstrated that much of this " junk DNA " is transcribed as noncoding RNAs (including microRNAs and lncRNAs). Together, these noncoding RNAs have been demonstrated to influence the expression of around 30% of protein-coding genes and have been demonstrated to play important homeostatic roles that act to normalize gene expression and maintain cellular phenotypes during development and disease. In this special issue focusing on noncoding RNAs, we bring together a collection of articles from various areas of diabetes and islet cell biology. T. Avnit-Sagi et al. and S. Kredo-Russo et al. discuss the regulation of two important pancreas-specific microRNAs, miR-7 and miR-375. Another article by A. D. Mandelbaum et al. describes how miRNAs can affect islet architecture. Research carried out in the past few years from several laboratories has clearly demonstrated that miRNAs and other noncoding RNAs are essential for development and differentiation of pancreatic progenitor cells as well as for …