Can we exploit mRNA modifications to control protein expression? Genes are encoded by DNA but are transcribed into a message called RNA before they can be translated into protein. RNA can be chemically modified at a gene-specific level, and this modification has been central to the success of RNA vaccines against COVID-19. Despite the importance of these modifications in cellular life and in biotechnology, the role of the most abundant RNA modifications is unclear. This project will investigate ....Can we exploit mRNA modifications to control protein expression? Genes are encoded by DNA but are transcribed into a message called RNA before they can be translated into protein. RNA can be chemically modified at a gene-specific level, and this modification has been central to the success of RNA vaccines against COVID-19. Despite the importance of these modifications in cellular life and in biotechnology, the role of the most abundant RNA modifications is unclear. This project will investigate how we can exploit RNA modifications to modulate protein expression in a tractable single-celled organism with a small genome, Plasmodium. This information is important because understanding gene regulation is fundamental to all life, and the role of RNA modifications is emerging as integral to biotechnology.Read moreRead less
Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.Read moreRead less