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RNA Secondary Structure Prediction Using High-throughput SHAPE
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Finding RNA structure in the unstructured RBPome.

Yaron Orenstein1, Uwe Ohler2, Bonnie Berger3,4

  • 1Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA, USA.

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|February 22, 2018
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Summary
This summary is machine-generated.

RNA structure significantly influences RNA-binding protein interactions, even in seemingly unstructured RNAs. This study reveals RNA structure

Keywords:
RBPRBPomeRNA structureRNA-binding proteinsRNAcompeteeCLIP

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Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Genomics

Background:

  • RNA-binding proteins (RBPs) are crucial for cellular processes, exhibiting diverse sequence and structure specificities.
  • Existing RNAcompete data primarily captures sequence specificities, with limited insight into structural preferences due to probe design.
  • Inferring structural binding models for a large number of RBPs has been a significant challenge.

Purpose of the Study:

  • To re-validate and uncover the role of RNA structure in the RBPome using the largest dataset to date.
  • To develop and apply novel computational methods for inferring RNA structure and binding preferences.
  • To enhance the prediction of RBP binding using structural information.

Main Methods:

  • Utilized the RCK algorithm to infer sequence and structural binding models from RNAcompete data.
  • Analyzed RNA structure variability in ostensibly unstructured RNA probes and correlated it with RBP binding.
  • Developed predictive models for RBP binding based on RNA structure and amino acid content.

Main Results:

  • Demonstrated that RNA structure exists and is variable in unstructured RNA probes, correlating with RBP binding.
  • Identified an overall preference for RBPs to bind RNA loops.
  • Significantly improved in vitro and in vivo RBP binding prediction accuracy by incorporating RNA structure.
  • Showed that RNA structural binding preferences can be inferred from protein amino acid composition alone.

Conclusions:

  • Transformed the RNAcompete compendium into a valuable resource for structure-based RBP binding models.
  • Highlighted the critical and previously underestimated role of RNA structure in protein-RNA interactions for hundreds of RBPs.
  • Enabled large-scale assessment of RNA structure's influence across the RBPome.