The Preiss Group is at the forefront of investigating RNA-level gene regulation in eukaryotes, a field of great significance due to the extensive transcription of our genome into diverse RNA molecules, many of which remain shrouded in mystery regarding their functions. Our overarching goal is to unravel the intricacies of transcription outputs, shedding light on how RNA processing, modification, and dynamic RNA-protein interactions shape the function of the transcriptome. Given the prevalence of RNA dysregulation in disease, our research addresses various facets of human health, with an emphasis on cancer and cardiac biology. Our research relies on mammalian and yeast cell culture models, employing a blend of classical molecular biology techniques and cutting-edge 'omics' approaches.

Much of our research revolves around messenger RNA (mRNA), which gained significant attention during the global COVID-19 pandemic due to the success of mRNA vaccines. mRNA holds the genetic code for protein synthesis, a process executed by the ribosome through initiation, elongation, and termination phases, each facilitated by distinct accessory factors. To gain deeper insights into the intricacies of mRNA translation mechanisms and their regulation by cellular signalling, RNA-binding proteins, and non-coding RNAs, we leverage specialised high-throughput sequencing techniques. Our contributions to understanding ribosome recruitment to mRNA during translation initiation are particularly noteworthy. We pioneered an innovative approach called "translation complex profile sequencing," related to the popular 'ribosome profiling' method. Additionally, we delved into how microRNAs influence translation initiation and how controlled transcription termination leads to the generation of mRNA isoforms, some of which are subjected to microRNA-mediated repression, while others evade it.

In the rapidly growing field of epitranscriptomics, which focuses on the functional analysis of RNA modifications, our group has played a pioneering role. We provided a first map of 5-methylcytosine in the human transcriptome, established its link to translation within mRNA molecules and are further exploring the enzymology and molecular function of 5-methylcytosine through ‘reader’, ‘writer’ and ‘eraser’ proteins.

Our fascination with circular RNAs, a surprisingly prevalent group of RNA molecules, has led us to investigate their unique biogenesis through 'back-splicing'. We now study their potential role as ‘molecular sponges’ and as unusual templates for protein synthesis.

Lastly, through the lens of proteomics, we are actively exploring the phenomenon of proteins that, in addition to their recognized functions, also bind RNA. This research has unveiled an unexpectedly frequent cross-talk between RNA biology and other cellular processes, including intermediary metabolism. We are now exploring, for selected examples, whether this means that a protein ‘moonlights’ to regulate its RNA-binding partner or whether the RNA regulates the protein’s already recognised function in a process termed ‘riboregulation’.

The Preiss Group is dedicated to advancing knowledge in these multifaceted areas of RNA biology. We enthusiastically welcome inquiries from prospective Honours or PhD students interested in joining our ongoing research projects.

Centres

• Director - The Shine-Dalgarno Centre for RNA Innovation