Abstract
T-box riboswitches constitute a large family of tRNA-binding leader sequences that play a central role in gene regulation in many gram-positive bacteria. Accurate inference of the tRNA binding to T-box riboswitches is critical to predict their cis-regulatory activity. However, there is no central repository of information on the tRNA binding specificities of T-box riboswitches, and de novo prediction of binding specificities requires advanced knowledge of computational tools to annotate riboswitch secondary structure features. Here, we present the T-box Riboswitch Annotation Database (TBDB, https://tbdb.io), an open-access database with a collection of 23,535 T-box riboswitch sequences, spanning the major phyla of 3,632 bacterial species. Among structural predictions, the TBDB also identifies specifier sequences, cognate tRNA binding partners, and downstream regulatory targets. To our knowledge, the TBDB presents the largest collection of feature, sequence, and structural annotations carried out on this important family of regulatory RNA.
Highlights
Bacteria exploit a wide-range of cis-acting RNA regulatory elements to control gene expression in response to specific environmental stimuli
In the gram-positive model organism Bacillus subtilis, an analysis of cis-regulatory sequences in the upstream region of several amino-acyl tRNA synthetase (ARS) genes revealed that non-amino-acylated tRNAs can act as a positive regulator [5,6]
Database entries are provided in a searchable, tabulated format
Summary
Bacteria exploit a wide-range of cis-acting RNA regulatory elements to control gene expression in response to specific environmental stimuli. In the gram-positive model organism Bacillus subtilis, an analysis of cis-regulatory sequences in the upstream region of several amino-acyl tRNA synthetase (ARS) genes revealed that non-amino-acylated tRNAs can act as a positive regulator [5,6] The discovery of this feedback loop was a breakthrough in understanding the expression of ARSs under nutrient limiting conditions. Additional Watson-Crick base pair between the tRNA acceptor arm (‘5-NCCA-3′) and the ‘T-box sequence’ (5′-UGGN-3′) was demonstrated to control regulatory logic (Figure 1B) [11,12] These interactions confer initial T-box specificity to its cognate tRNA. TBDB predicts putative transcriptional and translational T-box sequences, annotates secondary structures, identifies functional features and downstream genes, finds cognate pairs of tRNAs from host organisms, calculates MFE (minimum freeenergy) structures, and provides rich visualization for known and predicted T-box leader sequences (Figure 2). As a resource for the wider non-coding RNA community, the TBDB is the first structural and functionally annotated database for studying gene regulation by T-box riboswitches
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