The Preiss group studies the mechanisms and transcriptome-wide patterns of RNA-level gene regulation in eukaryotes, an area of strong general interest as much of our genome is transcribed into a myriad of RNAs, many with unknown functions. The general intent is to chart the complexity of such transcription outputs and how transcriptome function is shaped through RNA processing/modification and dynamic RNA-protein interactions. Dysregulation of RNA-level control abounds in disease; hence the group’s research addresses human health in diverse ways, with a particular emphasis on contributions to cancer and cardiac biology. The work is primarily based in mammalian and yeast cell culture models and employs a mix of classic molecular biology and contemporary ‘omics’ approaches.
One main focus is mRNA translation, a process that takes place on the ribosome and is divided into initiation, elongation and termination phases, each aided by numerous distinct accessory factors. The group uses specialised high-throughput sequencing methods to better understand the mechanism of translation and how it is regulated by cellular signalling, RNA-binding proteins and non-coding RNAs. For example, the group has made important contributions to the understanding of ribosome recruitment to mRNA during the initiation phase of translation. To achieve this, they innovated the sequencing and mapping of footprints of ribosomal complexes along mRNA; their approach, termed translation complex profile sequencing, is related to the popular ‘ribosome profiling’ method. They have also characterised how microRNAs repress translation initiation and how regulated transcription termination creates mRNA isoforms that are either subjected to, or evade, microRNA-mediated repression.
The group is further contributing to the bourgeoning epitranscriptomics field, concerned with the functional study of RNA modifications. Specifically, they pioneered the mapping of 5-methylcytosine in the human transcriptome and linked its presence in mRNA to translation. Their interest in the surprisingly prevalent group of circular RNAs, has led them to describe aspects of their unusual biogenesis through ‘back-splicing’ and their potential function in protein synthesis. Finally, using the tools of proteomics, the Preiss group is also on the hunt for proteins that, besides their recognised function, ‘moonlight’ in RNA-binding. This has revealed a surprisingly frequent crosstalk between RNA biology and other cellular processes such as intermediary metabolism.
The above-mentioned areas of RNA biology are all actively researched in the Preiss Group and enquiries for currently available projects are welcome from potential Honours or PhD students.
- How cells master the art of reading life's recipes 21 July 2016
- Protein insights to help find heart disease cure 26 July 2016
- New honour for ANU medical researcher 17 April 2016
- Unlocking the secrets of stem cell generation ANU media release and video clip
- Researchers identify stem cells that can be reprogrammed The Canberra Times 11 December 2014
- International study a major step forward in stem cell treatment research ABC Online 11 December 2014
- Australian researchers discover new ways to grow body parts for transplant ABC News 11 December 2014
- ANU role in stem cell research Canberra Times 11 December 2014
- Dr Jen Clancy and Professor Thomas Preiss have their paper featured on the cover of Nature Chemical Biology 2 May 2014
- Professor Thomas Preiss awarded The Julian Wells Medal at Lorne 17 February 2014
- Further information on the recent reprogramming papers
Research support officers
- Wagner S, Herrmannová A, Hronová V et al 2020 Selective Translation Complex Profiling Reveals Staged Initiation and Co-translational Assembly of Initiation Factor Complexes. Mol Cell, 79(4):546–560.e7
- Schumann U, Zhang HN, Sibbritt T et al 2020 Multiple links between 5-methylcytosine content of mRNA and translation. BMC Biol18:40
- Janin M, Ortiz-Barahona V, Castro de Moura M, et al 2019 Epigenetic Loss of Ribosomal RNA Methyltransferase NSUN5 in Glioma Drives a Stress Adaptive Translational Program. Acta Neuropathol, 2019; 135:601.
- Sen ND, Gupta N, Archer S, et al 2019 Functional interplay between DEAD-box RNA helicases Ded1 and Dbp1 in preinitiation complex attachment and scanning on structured mRNAs in vivo. Nucleic Acids Res ; 83:779.
- Ragan C, Goodall GJ, Shirokikh NE*, Preiss T*. 2019 Insights into the biogenesis and potential functions of exonic circular RNA. Sci Rep ; 9(1): 2048.
- Shirokikh NE, Dutikova J, Staroverova M, Hannan R, Preiss T. 2019 Migration of small ribosomal subunits on the 5' untranslated regions of capped messenger RNA Int J Mol Sci 20(18):4464.
- Bommer UA, Preiss T. Neue RNA-Moleküle und die Regulation der Genexpression auf Translationsebene. [New RNA molecules and regulation of gene expression at the level of translation.] BIOspektrum 2019; 25(3):350-351
- Janapala Y, Preiss T, ShirokikhN. 2019 Control of translation at the initiation phase during glucose starvation in yeast. Int J Mol Sci; 20(16):E4043.
- Swaminathan A, Harrison PA, Preiss T, Beilharz TH. 2019 PAT-Seq: A method for simultaneous quantitation of gene expression, poly(A)-site selection and poly(A)-length distribution in yeast transcriptomes. In: Oliver SG, Castrillo JI, eds. Methods Mol Biol
- Shirokikh NE, Archer SK, Beilharz TH, Powell D and Preiss T (2017) Translation complex profile sequencing to study the in vivo dynamics of mRNA-ribosome interactions during translation initiation, elongation and termination. Nature Protocols 12:697–731