Rnomics: RNA in mammalian evolution and development - John Mattick

Professor John Mattick

We are exploring the thesis that the genetic programming of higher organisms has been fundamentally misunderstood for the past 50 years, because of the assumption that most genetic information is transacted by proteins. It is now clear, despite the fact that only a small fraction encodes proteins, that the majority of the genomes of mammals and other complex organisms is transcribed in a developmentally-regulated manner, and that most complex genetic phenomena are RNA-directed. Working in conjunction with collaborators in the United States, Europe and Japan, we are working to characterise and understand the functions of the mammalian transcriptome, and to validate the prediction that most genetic information in mammals is conveyed by RNAs that control differentiation and development. This includes the identification of small RNAs that regulate gene expression at various levels, including transcription, and to determine the expression patterns and function of the tens of thousands of longer noncoding RNAs that are dynamically expressed during differentiation in mammalian cells, including embryonal stem cells. Among our recent findings we have shown that it is possible, if not likely, that most of the mammalian genome is under evolutionary selection, and demonstrated that the majority of long noncoding RNAs are expressed in the brain, many in precise cellular and subcellular locations, some of which are novel. We use advanced computational, visual and experimental methods, integrating in silico, in vitro and in vivo approaches. The outcomes of our research will be to expand our understanding of human evolution, genetics and development, with important practical implications in medicine, genetic engineering and programming of self-assembling systems.


Research projects

• Bioinformatic prediction and experimental validation of new classes of small RNAs in animals


• Analysis of the dynamic expression of long noncoding RNAs during the differentiation of embryonal stem cells, neural stem cells, muscle, macrophages, T-cells and developing tissues such as the male and female genital ridge, as well as the alteration of noncoding RNA expression in pathological states such as cancer


• Analysis of the subcellular location of noncoding RNAs to expand knowledge of existing cellular compartments and discover new ones


• Targeted functional analysing of selected non-coding RNAs involved in developmental processes and neurogenesis


• Analysis of the conservation patterns of noncoding regions in the mammalian genome and alignment on the basis of RNA structural rules


• Deep sequencing of the small and large RNA transcriptome in embryonal stem cells, and various tissues in mouse and human, as well as of RNAs associated with chromatin modification complexes, transcription factors, RNA editing enzymes and DNA:RNA triplex structures in chromatin

Key Publications

Amaral, P.P., Dinger, M.E., Mercer, T.R., and Mattick, J.S. (2008). The eukaryotic genome as an RNA machine. Science 319: 1787-1789.

Dinger, M.E., Amaral, P.P., Mercer, T.R., Pang, K.C., Bruce, S.J., Gardiner, B.B., Askarian-Amiri, M.E., Ru, K., Soldà, G., Simons, C., Sunkin, S.M., Crowe, M.L., Grimmond, S.M., Perkins, A.C., and Mattick, J.S. (2008). Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Research 18: 1433–1445.

Mercer, T.R., Dinger, M.E., Sunkin, S.M., Mehler, M.F., and Mattick, J.S. (2008). Specific expression of non-coding RNAs in mouse brain. Proceedings of the National Academy of Sciences USA 105: 716-721.

Mattick, J.S., and Mehler, M.F. (2008). RNA editing, DNA recoding and the evolution of human cognition. Trends in Neuroscience 31: 227-233.

Mattick, J.S. (2007). A new paradigm for developmental biology. Journal of Experimental Biology 210: 1526-1547.

Taft, R.J., Pheasant, M., and Mattick, J.S. (2007). The relationship between non-protein-coding DNA and eukaryotic complexity. Bioessays 29: 288-299.

Mattick, J.S., and Makunin, I.V. (2006). Non-coding RNA. Human Molecular Genetics 15: R17-R29.

Mattick, J.S., and Gagen, M.J. (2005). Accelerating networks. Science 307: 856-858.

Bejerano, G., Pheasant, M., Makunin, I., Stephen, S., Kent, W.J., Mattick, J.S., and Haussler, D. (2004). Ultra-conserved elements in the human genome. Science 304: 1321-1325.

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