MODOMICS: a database of RNA modification pathways

Abstract

MODOMICS is the first comprehensive database resource for systems biology of RNA modification. It integrates information about the chemical structure of modified nucleosides, their localization in RNA sequences, pathways of their biosynthesis and enzymes that carry out the respective reactions. MODOMICS also provides literature information, and links to other databases, including the available protein sequence and structure data. The current list of modifications and pathways is comprehensive, while the dataset of enzymes is limited to Escherichia coli and Saccharomyces cerevisiae and sequence alignments are presented only for tRNAs from these organisms. RNAs and enzymes from other organisms will be included in the near future. MODOMICS can be queried by the type of nucleoside (e.g. A, G, C, U, I, m1A, nm5s2U, etc.), type of RNA, position of a particular nucleoside, type of reaction (e.g. methylation, thiolation, deamination, etc.) and name or sequence of an enzyme of interest. Options for data presentation include graphs of pathways involving the query nucleoside, multiple sequence alignments of RNA sequences and tabular forms with enzyme and literature data. The contents of MODOMICS can be accessed through the World Wide Web at .

A chemical screen for biological small molecule–RNA conjugates reveals CoA-linked RNA

“…S9), as well as many species consistent with rRNA and tRNA nucleoside modifications (SI Appendix, Fig. S10) that have been previously reported, although not necessarily known to exist in E. coli or S. venezuelae (18). These results validate the ability of the nucleotide cleavage method to detect the presence of known small molecule-RNA conjugates.…”

“…In contrast with these newer insights into its functional diversity, the known chemical diversity of natural RNA has remained limited primarily to canonical polyribonucleotides, 3Ј-aminoacylated tRNAs (17), modified nucleobases in a variety of RNAs (18), and 5Ј-capped mRNAs in eukaryotes (19)(20). This disparity between functional and chemical diversity, coupled with the powerful functional properties of synthetic small molecule-nucleic acid conjugates (21)(22)(23)(24) led us to speculate that small molecule-RNA conjugates beyond those previously described may exist in modern cells as evolutionary fossils or even as novel RNAs with functions enabled by their modifications.…”

Chemical Modifications Mark Alternatively Spliced and Uncapped Messenger RNAs in Arabidopsis

“…Therefore, as a positive control verifying that HAMR was detecting bona fide modification sites in the Arabidopsis transcriptome, we derived "known" Arabidopsis tRNA modification sites as those with extensive homology to known modified sites in S. cerevisiae. Specifically, the yeast data were compiled from the Modomics database (Dunin-Horkawicz et al, 2006) and aligned to Arabidopsis tRNAs. Modifications within regions of homology were mapped from yeast to Arabidopsis using a custom pipeline incorporating tRNAscan (Lowe and Eddy, 1997) and LocARNA ) (see Methods) (Supplemental Files 1 and 2).…”

“…Each predicted modified base was then classified using nearestneighbor machine learning, as described previously (Ryvkin et al, 2013). Known tRNA modifications in Saccharomyces cerevisiae (from the MODOMICS database) (Dunin-Horkawicz et al, 2006) were used previously (Ryvkin et al, 2013) to construct the training set.…”

The 2′-O-methyltransferase responsible for modification of yeast tRNA at position 4

“…tRNA molecules are extensively modified relative to other classes of RNA. Indeed, 101 of 120 known RNA modifications are found in tRNA (Limbach et al 1994;Dunin-Horkawicz et al 2006), and mature nonorganeller tRNA contains an average of 9.3 modified residues (Sprinzl et al 1998). In the yeast Saccharomyces cerevisiae, 25 modifications have been found within the 34 sequenced cytoplasmic tRNAs, and the average tRNA bears z13 modifications (Limbach et al 1994;Sprinzl et al 1998).…”