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TRR 319:  RMaP: RNA Modification and Processing

Subject Area Biology
Medicine
Term since 2021
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 439669440
 
The life cycle of an RNA is a process of continuous maturation from transcription to degradation. Scientific research on this periodically produces breakthrough results that fundamentally change our scientific view on life. Now, for a little over a decade, RNA research has increasingly focused on the effect of RNA modifications, structural entities in RNA that do not conform to the four canonical nucleosides. More recently, RNA modifications themselves were at the center of a scientific breakthrough that affected more than our outlook on science and had significant societal impact. The corona pandemic boosted public interest into research on both viral RNA replication, and mRNA-based vaccines, both heavily influenced by RNA modifications. The fast ascent of RNA modifications points out gaps in our conceptual coverage of RNA maturation, specifically at intersections where events of modification and classical processing mutually affect each other. It is the declared goal of this research consortium on RNA Modification and Processing (RMaP) to elucidate such interplays on selected examples as well as on a principal basis. Our projects investigate RNA modifications in various RNA species and track their influence on processing events. Inversely, we also investigate processing events and their effects on RNA modification. The investigations cover the major RNA species involved in translation, mRNA, tRNA and rRNA, but also include small noncoding RNAs such as piRNA. For a comprehensive understanding of RNA maturation, we must inevitably refine the above definitions of modification and processing to a wider scope. RMaP seeks to promote an integrated view, including capping, phosphorylation, untemplated nucleotide additions, ligations and similar phenomena under the heading of processing. As a result of our own research, RMaP’s perception of RNA modifications in the larger sense goes beyond the by-now classical post-transcriptional deamination, isomerization, and transfer of chemical entities from typical metabolites to now include conjugation of larger entities such as entire proteins. We furthermore open our view towards chemical alterations to RNA and its modifications that do not originate from the directed action of dedicated proteins, such as damage to processed RNA and RNA modifications. The characteristics of RNA modifications necessitate sophisticated analytical methods as technological underpinnings, which can resolve structural details at the atomic level to identify, characterize and position modifications. RMaP develops methods in a dedicated technology section, which covers modification-aware sequencing, mass spectrometry, data science as well as a database and repository to support a global collection of research data related to RNA modification and processing.
DFG Programme CRC/Transregios

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Co-Applicant Institution Ruprecht-Karls-Universität Heidelberg
Participating Institution Deutsches Krebsforschungszentrum (DKFZ)
 
 

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