The hidden layer of regulatory RNAs in human development, physiology and disease — ASN Events
  1. Schedule
  2. ESA Plenary - The hidden layer of regulatory RNAs in human development, physiology and disease
  3. The hidden layer of regulatory RNAs in human development, physiology and disease

The hidden layer of regulatory RNAs in human development, physiology and disease (#137)

John S Mattick 1 , Timothy R Mercer 1 , Michael B Clark 2 , Marcel E Dinger 1
  1. Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
  2. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia

High throughput analyses have shown that the vast majority of the human genome is dynamically transcribed to produce a previously hidden universe of different classes of small and large, overlapping and interlacing intronic, intergenic and antisense non-protein-coding RNAs. The transcriptome is in fact far more complex than the genome, which is best viewed as a zip file that is unpacked in highly cell-specific patterns during development. This is illustrated by the use of targeted sequencing through RNA CaptureSeq1  to reveal thousands of previously unknown exons and spliced isoforms of oncogenes and tumour suppressors from Wellcome Trust Sanger Cancer Census gene loci, as well as at least 1500 new lncRNA genes in intergenic GWAS regions associated with complex diseases. These RNAs fulfill a wide range of regulatory functions, with miRNAs and related species being best (although not well) understood. The functions of the large/long noncoding RNAs (lncRNAs) are varied and include central roles in the formation of various differentiation-specific subnuclear organelles. However, recent evidence suggests that the major function of lncRNAs is to guide chromatin-modifying complexes to their sites of action, to specify the architectural trajectories of development. Not surprisingly, it is also emerging that variations in the sequence or expression of these RNAs not only underpin phenotypic differences between individuals and species, but also play significant roles in the etiology of complex diseases. Moreover, the emerging transcriptomic, epigenomic and nuclear structural data point to an extraordinary precision of the 4-dimensional organisation and expression of the genome that far exceeds current understanding. This system has also evolved plasticity, via RNA editing, which appears to be the molecular basis of environmental-epigenome interactions and brain function.2  

  1. Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA*, Mattick JS* and Rinn JL* (*Joint corresponding authors) (2012) Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nature Biotechnology 30: 99-104.
  2. Mattick JS (2011) The central role of RNA in human development and cognition. FEBS Letters 585: 1600–1616.
@ESASRB