The role of 5-methylcytosine in mammalian mRNA

The translation of genetic information stored in the DNA into proteins follows a complex series of events starting with the transcription of the DNA into messenger RNA, the correct processing of the messenger RNA (mRNA), the transport of the mRNA to the protein factories in the cell, the ribosomes, and finally, ending in the production of the protein according to the mRNA template. A multitude of regulatory mechanisms is required to ensure the perfect interplay between these events at any given time in the cell or in the life of an organism. One of these regulatory processes is the postsynthetic modification of the mRNA molecule. Thereby, the modification adds information regarding the subsequent fate of the RNA molecule, which is why it is frequently referred to as epitranscriptomic modification. The study of the epitranscriptome is an emerging field of research and although great progress has been made in recent years, there are many open questions. One of the aspects that remains underinvestigated is the functional significance of the observed methylation of cytosine bases in mRNA. With this research grant we will study the generation and function of cytosine methylation in mRNA. We will combine experiments in mammalian cells with in vitro analyses to examine the effect of m5C on several aspects of mRNA metabolism. With the experiments proposed here, we should be able to take a big step towards the elucidation of the molecular machineries involved in epitranscriptomic control. Such an understanding will not only contribute to expand our knowledge of fundamental cellular regulatory mechanisms at the level of RNA, it will have profound ramifications beyond basic research into a variety of research areas including human diseases whose etiology and pathology may involve as yet undiscovered epitranscriptomic aspects.