Introduction

Non-coding RNAs (ncRNAs) were found to be involved in many cellular processes from the gene transcriptional regulation to the catalysis of chemical reactions. Many ncRNAs, including cis-regulatory elements, are modular biomolecules, composed largely of recurrent structural motifs glued together via mutual interactions into a compact, functional, 3D structure.
RNA Bricks database provides information about the recurrent RNA motifs and their interactions, both with themselves and with proteins. In contrast to other similar tools (RNA 3D Motif Atlas, RNA Frabase, Rloom) here RNA motifs are presented in their natural environment, that is neighborhood of other molecules in a solution or in a crystal.

RNA Brick, what is that?

"RNA brick" is a set of interacting nucleotide residues from the same chain, flanked by WC or wobble base pairs. In particular we distinguish three types of RNA bricks or motifs. Stems are arrays of WC/wobble base pair tandems. Loops are motifs composed of single-stranded fragments flanked by WC/wobble pairs. Terminal fragments, or strands are single-stranded fragments with only one end involved in a WC/wobble pair.

How does it work?

The RNA structures stored in this database are coded in a form of graphs. Basic secondary structure motifs are represented as nodes. Black, grey and open circles denote stems, loops, and single stranded motifs respectively. If an RNA motif is in contact with a protein, corresponding node will be marked with a green circle.
The edges represent either bases shared by neighbor motifs (thick, grey lines), or tertiary contacts (thin red or blue lines). Red edges depict intramolecular contacts, blue crystallographic ones. If two motifs are both neighbors, and in tertiary or crystallographic contact, corresponding nodes will be linked with a thick edge of an appropriate color (red, or blue).

Please note that in RNA Bricks all contacts are treated equally. In particular a graph edge may represnt a signle h-bond, stacking, annotated basepair, or any combination of these contact types.

The graphs representing RNA structures are interactve and may be freely zoomed and moved. This feature is particularly useful in case of large RNA molecules with complex intercation networks (e.g. ribosomes)

Browsing structures

All listed entries can be browsed page by page, searched by keywords or filtered by Rfam/Uniprot IDs. Cliking on a molecular image or PDB ID in the left column (1) will display details of the given structure. Quality scores (2) represent an average reliability of a given structure RNA content. See Quality scores section for details.

Browsing motifs

One can select RNA motifs clicking directly on the graph (3) or selecting row in a table (1). Selected motifs may be visualized in Jmol by clicking on the "show in jmol" link (2).

The interactive table is composed of the following columns:

Secondary strcuture

Secondary strucutre graphs are based on MC-Annotate analysis. Nucleotides with green halos are in contact with a protein.

Fragment residues

This column lists residues from continuous chain segments forming a given motif. You can query for motifs with "chain id/residue id"

download - get a motif coordinates, sequence, list of h-bonds, and annotated base-pairs

search - use a motif as a RNA Bricks search query (structure, or sequence based)

Similar motifs

This column lists number of similar motifs at 1.0Å backbone RMSD. Click on a link to switch to the cluster view.

Contacts

This column lists motif neighbors (grouped by type). If a given motif forms annotated contacts with other RNA motifs, their names will be listed explicitly (4). You can click on these to see 2D diagram of an intercation.

Quality

Quality scores calculated for separate motifs. See Quality scores section for details.

Browsing clusters

Jmol applet on the right side of the clustrer view displays superposition of motifs selected in a table (1). Columns (2) and (3) list links to PDB structures containig selected motifs, and detailed information about a motif environment.

Selected motifs can be downloaded with link (5). A snapshot of current Jmol view can be taken with link (6). Quality scores listed in column (4) depict reliability of separate motifs. See Quality scores section for details.

Quality scores

RNA Bricks provide the following quality validation scores

clashes - a number of bad non-H-bond overlaps (0.4 Å or greater) per 1000 atoms. This score was determined with the Probe program from Molprobity suite.

geometry - a fraction of nucleotides with suspicious backbone torsion angles, that is not within a set of 54 favorable RNA backbone conformer defined by the RNA Ontology Consortium. This score was determined with the use of Suitename program from Molprobity suite.

e-density - a fraction of nucleotides with poor electron density. This score was derived from experimental structure factors deposited in PDB. Poor electron density means either weak signal (below 1 σ on average) or real-space correlation coefficients value below 0.7

All the above described scores are available on three scales

structure reliability - these scores reflect an average reliability of an RNA content of a given PDB structure

motif reliability - these scores are calculated for separate motifs and represent their average reliability

nucleotide reliability - this is a most detailed quality information available. In the Jmol view atoms forming bad clashes, nucleotides with suspicious backbone geometry or weak electron density can be marked with black halos.

Viewing RNA 3D motifs with Jmol

Selected motifs are dislayed in warm colors (red, orange, yelow, brown etc.). The Jmol applet provides followoing visualization options:

Display RNA - display motifs that are in contact with selected motifs within Asymmetric Unit (colorcode: grey)

Display RNA (symm) - display motifs that form crystallographic contacts with selected motifs (colorcode: blue)

Display protein - display trace of protein chains that are in contact with selected motifs. The protein chains that form crystallographic conatcts are transparent (colorcode: green)

Display complete RNA - display phosphate atoms trace of a whole RNA chains related to the selected motifs (colorcode; grey)

Display others - display selected motifs neighbors that are neither water/ion, nor protein

Display contacts - display h-bonds and residues that are in contact with selected motifs

Show hydrogens - display hydrogen atoms. These were added with Reduce program if not present in the original file.

Quality scores - mark residues with poor quality scores (see Quality scores section for details)

Authors and contact

RNA Bricks database was developed by Grzegorz Chojnowski, Tomek Waleń, and Janusz Bujnicki. Feel free to contact us at gcho...@genesilico.pl with any comments, suggestions or bug-reports.

References

If you find this tool useful please cite:
Chojnowski G, Waleń T, and Bujnicki JM
RNA Bricks—a database of RNA 3D motifs and their interactions
Nucleic Acids Research, 2013, 1–9 doi:10.1093/nar/gkt1084 [Epub 2013 Nov 13] [pdf]

Tutorials

Working with the RNA Bricks interface

In this tutorial you will learn how to use the RNA Bricks web interface.

Quality scores in RNA Bricks

This tutorial presents the structure quality scores available in RNA Bricks.

Basic usage of the 3D search engine

RNA Bricks database provides a simple clustering method that groups RNA motifs with the same secondary structure and number of ribonucleotide residues. Therefore in some cases two motifs that have similar tertiary structures are classified to separate clusters due to differences in secondary structure annotation and/or presence of variable loops.
With this tutorial you will learn how to to query the database for all RNA 3D motifs that share common substructures with a motif of interest.

Advandced usage of the 3D search engine

This tutorial shows how to build advanced RNA Bricks 3D search engine queries. In particular you will learn how to search for RNA 3D motifs that share common substructure.

Troubleshooting

Jmol applet doesn't work

First test your java installation at www.java.com. If you can see a test applet, you probably encountered a rare RNA Bricks bug. Please let us know about it gcho...@genesilico.pl

Engine version: 18.04.2014