A Complex Network of Factors with Overlapping Affinities Represses Splicing Through Intronic Elements

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2012 Dec 18

PMID 23241926

Citations 67

Authors

Yang Wang

Xinshu Xiao

Jianming Zhang

Rajarshi Choudhury

Alex Robertson

Kai Li

Meng Ma

Christopher B Burge

Zefeng Wang

Affiliations

Soon will be listed here.

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.

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