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Research in our Group

Research in the Rentmeister group focuses on RNA at the interface of chemistry and biochemistry. We aim to understand mechanisms and control processes governing mRNA expression and turnover. To address these fundamental problems, we take a chemical perspective and develop chemical and chemo-enzymatic tools for manipulation, analysis, and control of mRNA at the molecular level. Our broad methodological scope – comprising purely chemical as well as chemo-enzymatic approaches –allows us to choose the best strategy to achieve our goals, independent of the specific tool. Importantly, our work does not stop at chemical synthesis. We strive to implement chemical modifications in living human cells and push the limits further to applications in vivo. Our group has a track record of research in RNA chemical biology, cofactor and protein engineering.

MePMe-seq: antibody-free simultaneous m6A and m5C mapping in mRNA by metabolic propargyl labeling and sequencing

Nov 7. 2023, https://doi.org/10.1038/s41467-023-42832-z

MePMe-seq

We developed MePMe-seq as a chemical biology method for simultaneous identification of mRNA methylations. We mapped N6-methyladenosine (m6A) and 5-methylcytidine (m5C) transcriptome-wide with single-nucleotide resolution. Our approach is independent of antibodies  and sequence motifs. It relies on metabolic labeling with a clickable methionine analogue called propargyl-selenohomocysteine (PSH) and the intercellular formation of the corresponding AdoMet analogue. 

 

Click chemistry allows for enrichment of methyltransferase targets. In combination with mRNA isolation and arrests of reverse transcription at the modified site, we can determine m6A and m5C  sites with high precision in the same sequencing runs.

Deciphering mRNA modifications
on a transcriptome-wide scale

The Rentmeister group focuses on chemical modifications of mRNA, a key aspect of epitranscriptomics. Our research aims to elucidate the functions of modified DNA and RNA bases to decrypt the chemical information level of nucleic acids beyond sequence information. We have developed innovative approaches such as MePMe-seq and CAPturAM, which enable precise mapping and identification of RNA modifications and methyltransferase targets, advancing our understanding of the regulatory functions of RNA modifications in gene expression.

SAM Analogues & protein engineering

By developing and applying S-Adenosyl-L-methionine (SAM) analogues, our research investigates biochemical processes, with a particular focus on DNA and RNA methylation. We engineer methionine adenosyltransferase (MAT) enzymes to produce SAM analogues with extended side chains and photocleavable groups, allowing for the selective labeling, enrichment, and controlled activation of biomolecules. These innovative SAM analogues enable precise modifications and advanced studies of methyltransferase targets and their roles in cellular regulation.

Synthetic 5′ caps and mRNA engineering

We concentrate on advancing mRNA engineering to boost its therapeutic potential, especially for vaccines, cancer immunotherapies, protein-supplement therapies, and genome editing. We aim to control mRNA activities at the molecular level by developing new synthetic 5′-capped mRNAs and chemical biology tools for precise identification of RNA modification sites. A key innovation, FlashCap, allows light-induced mRNA translation, providing spatio-temporal control over mRNA expression and offering a significant advancement in targeted gene expression studies and mRNA-based therapeutic strategies.

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