A systematic approach to RNA-associated motif discovery

Authors

Tian Gao, University of Nebraska-LincolnFollow
Jiang Shu, University of Nebraska-LincolnFollow
Juan Cui, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2018

Citation

Gao et al. BMC Genomics (2018) 19:146

doi 10.1186/s12864-018-4528-x

Comments

Copyright © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License

Abstract

Background: Sequencing-based large screening of RNA-protein and RNA-RNA interactions has enabled the mechanistic study of post-transcriptional RNA processing and sorting, including exosome-mediated RNA secretion. The downstream analysis of RNA binding sites has encouraged the investigation of novel sequence motifs, which resulted in exceptional new challenges for identifying motifs from very short sequences (e.g., small non-coding RNAs or truncated messenger RNAs), where conventional methods tend to be ineffective. To address these challenges, we propose a novel motif-finding method and validate it on a wide range of RNA applications.

Results: We first perform motif analysis on microRNAs and longer RNA fragments from various cellular and exosomal sources, and then validate our prediction through literature search and experimental test. For example, a 4 bp-long motif, GUUG, was detected to be responsible for microRNA loading in exosomes involved in human colon cancer (SW620). Additional performance comparisons in various case studies have shown that this new approach outperforms several existing state-of-the-art methods in detecting motifs with exceptional high coverage and explicitness.

Conclusions: In this work, we have demonstrated the promising performance of a new motif discovery approach that is particularly effective in current RNA applications. Important discoveries resulting from this work include the identification of possible RNA-loading motifs in a variety of exosomes, as well as novel insights in sequence features of RNA cargos, i.e., short non-coding RNAs and messenger RNAs may share similar loading mechanism into exosomes. This method has been implemented and deployed as a new webserver named MDS2 which is accessible at http://sbbi-panda.unl.edu/MDS2/, along with a standalone package available for download at https://github.com/sbbi/MDS2 .