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 http://genesilico.pl/modomics/.

Figure 1

A subgraph of adenosine modifications, showing the pathways of m¹Im synthesis (14). Experimentally verified reactions catalyzed by known enzymes from the MODOMICS dataset are indicated by solid arrows, putative reactions or those catalyzed by unknown enzymes are indicated by broken arrows (in this example: m¹I→m¹Im). The phylogenetic occurrence of nucleosides is shown by colored letters: Archaea (red A), Bacteria (blue B) and Eukaryota (green E).

Figure 2

Reaction panel illustrates the methylation of inosine (I) to N¹-methylinosine (m¹I) catalyzed by the Trm5p enzyme at the position 37 of the anticodon loop of tRNA^Ala (anticodon IGC), which also introduces the m¹G modification in a larger subset of other yeast tRNAs (15). The hyperlink to the G→m¹G reaction reveals a similar panel (data not shown) with Trm5p, as well as three other enzymes, namely tRNA MTases Trm10p in S.cerevisiae (16) and TrmD (17), and rRNA MTase RlmA(I) (18) (both in E.coli). Note that in Archaeal tRNAs, the enzymatic formation of m¹I, which exclusively occurs at the position 57 of the Ψ-loop, follows a completely different metabolic route [data not shown, for details see (14,19)].