Identification of 3D motifs in Rfam with JAR3D

Abstract

Many non-protein-coding RNAs have been discovered and more are being discovered each year. At first we know them only by their sequences in a few organisms, but to understand their function and interactions, we need to understand what 3D structures they may form, in whole or in part. Many hairpin and internal loops are known to form structured 3D motifs, many of which are recurrent across different non-coding RNAs, for example, kink turn and sarcin-ricin internal loops, and GNRA, UNCG, and T-loop hairpin loops. As such, a new non-protein-coding RNA may well have one or more known structured 3D loop motifs. The goal of this paper is to introduce a tool which can identify loops in Rfam seed alignments that match well to known 3D loop motifs, and which makes those identifications easily accessible. JAR3D was developed to map sequences of hairpin and internal loops to known 3D motifs, and was extended for this work to 3-way and 4-way junction motifs. We applied JAR3D to 4,166 Rfam seed alignments from Rfam 15.0 and made the results accessible on the JAR3D web page, which makes it easy to inspect and evaluate the possible matches for each loop in each Rfam family. We provide several examples which validate JAR3D's ability to identify the correct loop motif, using 3D structures of RNAs outside of the training set. We created a new page to search for instances of a particular loop motif across all Rfam families, to facilitate studies of how widespread the occurrence of each motif is. We provide statistics on how many Rfam loops appear to match well to a known 3D motif. Match rates are much higher for internal loops than for hairpins or multi-helix junctions.