Abstract for presentation at 11th International Congress of Human Genetics

Bioinformatic identification and experimental validation of functional noncoding RNAs

  • Dr Marcel Dinger, Institute for Molecular Bioscience, University of Queensland, St. Lucia QLD 4072, Australia
  • Dr Evgeny Glazov, Institute for Molecular Bioscience, University of Queensland, St. Lucia QLD 4072, Australia
  • Dr Ken Pang, Ludwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg VIC 3084, Australia
  • Dr Michael Pheasant, Institute for Molecular Bioscience, University of Queensland, St. Lucia QLD 4072, Australia
  • Dr Larry Croft, Institute for Molecular Bioscience, University of Queensland, St. Lucia QLD 4072, Australia
  • Prof John Mattick, Institute for Molecular Bioscience, University of Queensland, St. Lucia QLD 4072, Australia

    • The available evidence suggests that the evolution of multicellular organisms has been accompanied, and indeed empowered, by a massive increase in the utilization of noncoding RNAs to regulate and integrate complex networks of gene activity. Noncoding RNAs (ncRNAs) dominate the transcriptional output of the human genome, and most of the complex genetic phenomena in the higher organisms, including epigenetic memory, appear to connected to RNA signaling pathways. The available evidence also suggests that most known functional ncRNAs (such as miRNAs, siRNAs and snoRNAs) operate through sequence-specific recognition of other RNAs and DNA (i.e. as digital signals) to produce complexes that are in turn recognized and acted upon by generic infrastructural proteins to convert these signals to appropriate analog actions, such as translational repression, mRNA destruction, RNA modification, chromatin remodeling and (most likely) alternative splicing. Sequence-specific recognition allows the opportunity to develop bioinformatic strategies to identify these signals and their targets, a technique that has already been widely used in the case of miRNAs. We discuss the design issues involved, including the use of various rules for RNA:RNA and RNA:DNA interactions and other features / filters, and demonstrate these by the identification of large numbers of new snoRNAs in silico, a significant subset of which have been tested and validated in vivo. We provide evidence that there are many more small regulatory RNAs (including miRNAs) than has been previously thought or observed. We have also developed new microarray chips for high-throughput analysis of ncRNAs, which reveal dynamic changes of ncRNA expression during T-cell, muscle cell, and embryonal cell differentiation. Finally we discuss the genetic and experimental challenges of identifying and understanding the hidden layer of RNA regulatory networks that underpin human development and phenotypic variation.

    Conference Organiser - ICMS Pty Ltd