SSMART: sequence-structure motif identification for RNA-binding proteins

Bioinformatics. 2018 Dec 1;34(23):3990-3998. doi: 10.1093/bioinformatics/bty404.

Abstract

Motivation: RNA-binding proteins (RBPs) regulate every aspect of RNA metabolism and function. There are hundreds of RBPs encoded in the eukaryotic genomes, and each recognize its RNA targets through a specific mixture of RNA sequence and structure properties. For most RBPs, however, only a primary sequence motif has been determined, while the structure of the binding sites is uncharacterized.

Results: We developed SSMART, an RNA motif finder that simultaneously models the primary sequence and the structural properties of the RNA targets sites. The sequence-structure motifs are represented as consensus strings over a degenerate alphabet, extending the IUPAC codes for nucleotides to account for secondary structure preferences. Evaluation on synthetic data showed that SSMART is able to recover both sequence and structure motifs implanted into 3'UTR-like sequences, for various degrees of structured/unstructured binding sites. In addition, we successfully used SSMART on high-throughput in vivo and in vitro data, showing that we not only recover the known sequence motif, but also gain insight into the structural preferences of the RBP.

Availability and implementation: SSMART is freely available at https://ohlerlab.mdc-berlin.de/software/SSMART_137/.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Computational Biology
  • Nucleotide Motifs*
  • RNA*
  • RNA-Binding Proteins / chemistry*
  • Sequence Analysis, RNA
  • Software

Substances

  • RNA-Binding Proteins
  • RNA