SFB 1309 Research Areas
Area B: Modifications on Proteins
Project B03 – The role of RNA Methylation in centromeric R-loop formation
We developed a versatile proximity biotinylation method to label proteins and RNA in defined chromosomal regions and used it to characterize the proteomic composition of the centromere, a key chromatin domain defined by the centromeric H3 variant CenH3. Using this method, we discovered that centromere-associated RNA is enriched in methylated RNA that forms stable R-loops within repetitive DNA. In the next funding period, we will dissect how RNA methylation and R-loop formation regulate centromere function, combining in vitro and in vivo approaches in Drosophila as well as Human cells. Together with the Huc group we will test whether synthetic R-loop mimics can be used to interfere with (neo)centromere formation, a common contributor to genomic instability. Together, these studies will reveal mechanistic links between centromeric transcription, RNA methylation, R-loops, and Cen3 deposition, advancing understanding of genome stability, cancer biology, and speciation.
