Experience with German Research Consortia in the Field of Chemical Biology of Native Nucleic Acid Modifications.

The chemical biology of native nucleic acid modifications has seen an intense upswing, first concerning DNA modifications in the field of epigenetics and then concerning RNA modifications in a field that was correspondingly rebaptized epitranscriptomics by analogy. The German Research Foundation (DFG) has funded several consortia with a scientific focus in these fields, strengthening the traditionally well-developed nucleic acid chemistry community and inciting it to team up with colleagues from the life sciences and data science to tackle interdisciplinary challenges. This Perspective focuses on the genesis, scientific outcome, and downstream impact of the DFG priority program SPP1784 and offers insight into how it fecundated further consortia in the field.

Antibiotic profiling of wild-type bacilli led to the discovery of new lanthipeptide subtilin-producing Bacillus spizizenii strains whose 16S rDNA sequences differ from the B. spizizenii typing strain.

Two dozen field-collected Bacillus and a dozen Bacillus spizizenii wild-type strains from strain collections were selected on the basis of their antagonistic properties against the Gram-positive strain Micrococcus luteus. Based on their genetic and antibiotic profiles, they were characterized (subtilin encoding spaS gene sequences, mass spectrometric, and quantitative-reversed phase liquid chromatographic analyses, as well as the presence of the lanthionine cyclase protein SpaC by western blotting), seven novel producers of the lanthipeptide subtilin. Phylogenetic analyses of the subtilin-producing wild-type strains based on their 16S rRNA sequences showed that all seven strains could be classified as B.

Chemical Modifications of Ribosomal RNA.

Cellular RNAs in all three kingdoms of life are modified with diverse chemical modifications. These chemical modifications expand the topological repertoire of RNAs, and fine-tune their functions. Ribosomal RNA in yeast contains more than 100 chemically modified residues in the functionally crucial and evolutionary conserved regions.

Identification of the 3-amino-3-carboxypropyl (acp) transferase enzyme responsible for acp3U formation at position 47 in Escherichia coli tRNAs.

tRNAs from all domains of life contain modified nucleotides. However, even for the experimentally most thoroughly characterized model organism Escherichia coli not all tRNA modification enzymes are known. In particular, no enzyme has been found yet for introducing the acp3U modification at position 47 in the variable loop of eight E.

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program.

Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine.