Introduction

Sequence-specific interactions of RNA-binding proteins (RBPs) with their target transcripts are essential for post-transcriptional gene expression regulation in mammals. However, accurate prediction of RBP motif sites has been difficult because many RBPs recognize short and degenerate sequences. Here we describe a hidden Markov model (HMM)-based algorithm mCarts to predict clustered functional RBP-binding sites by effectively integrating the number and spacing of individual motif sites, their accessibility in local RNA secondary structures and cross-species conservation. This algorithm learns and quantifies rules of these features, taking advantage of a large number of in vivo RBP-binding sites obtained from cross-linking and immunoprecipitation data. We applied this algorithm to study two representative RBP families, Nova and Mbnl, which regulate tissue-specific alternative splicing through interacting with clustered YCAY and YGCY elements, respectively, and predicted their binding sites in the mouse transcriptome. Despite the low information content in individual motif elements, our algorithm made specific predictions for successful experimental validation. Analysis of predicted sites also revealed cases of extensive and distal RBP-binding sites important for splicing regulation. This algorithm can be readily applied to other RBPs to infer their RNA-regulatory networks. The software is freely available at http://zhanglab.c2b2.columbia.edu/index.php/MCarts.

Publications

  1. Prediction of clustered RNA-binding protein motif sites in the mammalian genome.
    Cite this
    Zhang C, Lee KY, Swanson MS, Darnell RB, 2013-08-01 - Nucleic acids research

Credits

  1. Chaolin Zhang
    Developer

    Laboratory of Molecular Neuro-Oncology, Howard Hughes Medical Institute

  2. Kuang-Yung Lee
    Developer

  3. Maurice S Swanson
    Developer

  4. Robert B Darnell
    Investigator

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Summary
AccessionBT006538
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesPerl
User InterfaceTerminal Command Line
Download Count0
Submitted ByRobert B Darnell