Discovering Ordered Motif Combinations in EZH2 Interacting Long Non-coding RNAs

Abstract Background EZH2 is linked to cancer, interacting in various ways with some long non-coding RNAs but not others. It is reasonable to assume that the interacting sequences have physical interaction sites which are not present in the non-interacting ones. We hypothesise that these interaction sites correspond to motifs (short subsequences) which appear in a particular order. We have developed software to find such ordered motif combinations. The software can also suggest where larger scale similarities between and within lncRNAs may be found by calculating mean information content. Results We investigated motifs of length 5 to 11, with up to 3 motifs per combination, in murine lncRNAs. Appearing in 13 out of 59 interacting lncRNAs, 4 combinations comprising 2 motifs of length 6 have been identified as EZH2 interaction site candidates which can be further investigated. Conclusions Our predictions can be tested experimentally to ascertain whether or not these combinations really do constitute interaction sites. For example, genome editing can be employed to measure the cellular and molecular effects of ablating these sequences in the EZH2-interacting lncRNAs. In addition, computational and advanced microscopy methodologies can be employed to locate these motifs within the tri-dimensional structure of these lncRNAs.