Introduction

Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an active mode of splicing regulation. Similarly to exon-proximal sites, distal sites contain evolutionarily conserved GCATG sequences and are associated with AS activation and repression upon modulation of Rbfox abundance in human and mouse experimental systems. As a proof of principle, we validated the activity of two specific Rbfox enhancers in KIF21A and ENAH distal introns and showed that a conserved long-range RNA-RNA base-pairing interaction (an RNA bridge) is necessary for Rbfox-mediated exon inclusion in the ENAH gene. Thus we demonstrate a previously unknown RNA-mediated mechanism for AS control by distally bound RNA-binding proteins.

Publications

  1. Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges.
    Cite this
    Lovci MT, Ghanem D, Marr H, Arnold J, Gee S, Parra M, Liang TY, Stark TJ, Gehman LT, Hoon S, Massirer KB, Pratt GA, Black DL, Gray JW, Conboy JG, Yeo GW, 2013-12-01 - Nature structural & molecular biology

Credits

  1. Michael T Lovci
    Developer

    1] Department of Cellular and Molecular Medicine, University of California, United States of America

  2. Dana Ghanem
    Developer

  3. Henry Marr
    Developer

  4. Justin Arnold
    Developer

  5. Sherry Gee
    Developer

  6. Marilyn Parra
    Developer

  7. Tiffany Y Liang
    Developer

  8. Thomas J Stark
    Developer

  9. Lauren T Gehman
    Developer

  10. Shawn Hoon
    Developer

  11. Katlin B Massirer
    Developer

  12. Gabriel A Pratt
    Developer

  13. Douglas L Black
    Developer

  14. Joe W Gray
    Developer

  15. John G Conboy
    Developer

  16. Gene W Yeo
    Investigator

Community Ratings

UsabilityEfficiencyReliabilityRated By
0 user
Sign in to rate
Summary
AccessionBT006788
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByGene W Yeo