A complex network of factors with overlapping affinities represses splicing through intronic elements
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Burge_A complex network.pdf
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Author(s)
Wang, Yang
Xiao, Xinshu
Zhang, Jianming
Choudhury, Rajarshi
Li, Kai
Ma, Meng
Wang, Zefeng
Robertson, Alex De Jong
Burge, Christopher B
Date Issued
December 2012
Journal
Nature Structural & Molecular Biology
Publisher
Nature Publishing Group
Citation
Wang, Yang, Xinshu Xiao, Jianming Zhang, Rajarshi Choudhury, Alex Robertson, Kai Li, Meng Ma, Christopher B Burge, and Zefeng Wang. “A complex network of factors with overlapping affinities represses splicing through intronic elements.” Nature Structural & Molecular Biology 20, no. 1 (December 16, 2012): 36-45.
Version
Author's final manuscript
Abstract
To better understand splicing regulation, we used a cell-based screen to identify ten diverse motifs that inhibit splicing from introns. Motifs were validated in another human cell type and gene context, and their presence correlated with in vivo splicing changes. All motifs exhibited exonic splicing enhancer or silencer activity, and grouping these motifs according to their distributions yielded clusters with distinct patterns of context-dependent activity. Candidate regulatory factors associated with each motif were identified, to recover 24 known and new splicing regulators. Specific domains in selected factors were sufficient to confer intronic-splicing-silencer activity. Many factors bound multiple distinct motifs with similar affinity, and all motifs were recognized by multiple factors, which revealed a complex overlapping network of protein-RNA interactions. This arrangement enables individual cis elements to function differently in distinct cellular contexts, depending on the spectrum of regulatory factors present.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1038/nsmb.2459
