title: A combined sequence and structure based method for discovering enriched motifs in RNA from in vivo binding data.
abstract: RNA binding proteins (RBPs) play an important role in regulating many processes in the cell. RBPs often recognize their RNA targets in a specific manner. In addition to the RNA primary sequence, the structure of the RNA has been shown to play a central role in RNA recognition by RBPs. In recent years, many experimental approaches, both in vitro and in vivo, were developed and employed to identify and characterize RBP targets and extract their binding specificities. In vivo binding techniques, such as CrossLinking and ImmunoPrecipitation (CLIP)-based methods, enable the characterization of protein binding sites on RNA targets. However, these methods do not provide information regarding the structural preferences of the protein. While methods to obtain the structure of RNA are available, inferring both the sequence and the structure preferences of RBPs remains a challenge. Here we present SMARTIV, a novel computational tool for discovering combined sequence and structure binding motifs from in vivo RNA binding data relying on the sequences of the target sites, the ranking of their binding scores and their predicted secondary structure. The combined motifs are provided in a unified representation that is informative and easy for visual perception. We tested the method on CLIP-seq data from different platforms for a variety of RBPs. Overall, we show that our results are highly consistent with known binding motifs of RBPs, offering additional information on their structural preferences.
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; Vavilov Institute of General Genetics, Russian Academy of Science, Moscow 11933, Russia.
authors.forename: Maya
authors.initials: M
authors.lastname: Polishchuk
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Paz
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Refael
authors.initials: R
authors.lastname: Kohen
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Rona
authors.initials: R
authors.lastname: Mesika
authors.affiliation: Faculty of Computer Science, Technion-Israel Institute of Technology, Haifa 32000, Israel; School of Computer Science, Herzliya Interdisciplinary Center, Herzliya 46150, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; Faculty of Computer Science, Technion-Israel Institute of Technology, Haifa 32000, Israel. Electronic address: yaelmg@tx.technion.ac.il.
authors.forename: Yael
authors.initials: Y
authors.lastname: Mandel-Gutfreund
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D066264:Datasets as Topic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D047468:Immunoprecipitation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods / Q000706:statistics & numerical data*; D012984:Software; D059467:Transcriptome
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA
keywords: CLIP-seq; Computational ranked based approach; Motif enrichment; RNA binding proteins; RNA secondary structure; RNA sequence and structure motifs; SMARTIV