Abstract
In recent years, hundreds of novel RNA-binding proteins (RBPs) have been identified, leading to the discovery of novel RNA-binding domains. Furthermore, unstructured or disordered low-complexity regions of RBPs have been identified to play an important role in interactions with nucleic acids. However, these advances in understanding RBPs are limited mainly to eukaryotic species and we only have limited tools to faithfully predict RNA-binders in bacteria. Here, we describe a support vector machine-based method, called TriPepSVM, for the prediction of RNA-binding proteins. TriPepSVM applies string kernels to directly handle protein sequences using tri-peptide frequencies. Testing the method in human and bacteria, we find that several RBP-enriched tri-peptides occur more often in structurally disordered regions of RBPs. TriPepSVM outperforms existing applications, which consider classical structural features of RNA-binding or homology, in the task of RBP prediction in both human and bacteria. Finally, we predict 66 novel RBPs in Salmonella Typhimurium and validate the bacterial proteins ClpX, DnaJ and UbiG to associate with RNA in vivo.
Highlights
Gene regulation in eukaryotes occurs at several levels and involves the action of transcription factors, chromatin, RNA-binding proteins (RBPs) and other RNAs
We show that TriPepSVM performs better than other methods in RBP prediction in human and the bacteria Escherichia coli and Salmonella Typhimurium
We propose TriPepSVM, a support vector machine (SVM)-based model to discriminate RNA-binding proteins from non-RNA binders based on the amino acid sequence of the protein of interest
Summary
Gene regulation in eukaryotes occurs at several levels and involves the action of transcription factors, chromatin, RNA-binding proteins (RBPs) and other RNAs. RIC utilizes UV cross-linking to induce stable RNA-protein interactions in living cells, followed by poly(A) RNA selection via magnetic oligo d(T) beads and subsequent protein identification by massspectrometry. Among them we find enzymes, cell cycle regulators and dual specificity DNA–RNA binders, including transcription factor and chromatin components [3]. The discovery of these unconventional RBPs without known RNAbinding motifs suggests the existence of new modes of RNA binding and the involvement of RBPs in previously unexplored biological processes [10]
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