IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v444y2006i7119d10.1038_nature05304.html
   My bibliography  Save this article

An RNA map predicting Nova-dependent splicing regulation

Author

Listed:
  • Jernej Ule

    (Howard Hughes Medical Institute
    Laboratory of Molecular Neuro-Oncology
    MRC Laboratory of Molecular Biology)

  • Giovanni Stefani

    (Howard Hughes Medical Institute
    Laboratory of Molecular Neuro-Oncology
    Yale University)

  • Aldo Mele

    (Howard Hughes Medical Institute
    Laboratory of Molecular Neuro-Oncology)

  • Matteo Ruggiu

    (Howard Hughes Medical Institute
    Laboratory of Molecular Neuro-Oncology)

  • Xuning Wang

    (Biocomputing, Information Technology)

  • Bahar Taneri

    (The Rockefeller University
    UCSD, Scripps Institution of Oceanography, Scripps Genome Center
    Eastern Mediterranean University)

  • Terry Gaasterland

    (The Rockefeller University
    UCSD, Scripps Institution of Oceanography, Scripps Genome Center)

  • Benjamin J. Blencowe

    (University of Toronto)

  • Robert B. Darnell

    (Howard Hughes Medical Institute
    Laboratory of Molecular Neuro-Oncology)

Abstract

Nova proteins are neuron-specific alternative splicing factors. We have combined bioinformatics, biochemistry and genetics to derive an RNA map describing the rules by which Nova proteins regulate alternative splicing. This map revealed that the position of Nova binding sites (YCAY clusters) in a pre-messenger RNA determines the outcome of splicing. The map correctly predicted Nova’s effect to inhibit or enhance exon inclusion, which led us to examine the relationship between the map and Nova’s mechanism of action. Nova binding to an exonic YCAY cluster changed the protein complexes assembled on pre-mRNA, blocking U1 snRNP (small nuclear ribonucleoprotein) binding and exon inclusion, whereas Nova binding to an intronic YCAY cluster enhanced spliceosome assembly and exon inclusion. Assays of splicing intermediates of Nova-regulated transcripts in mouse brain revealed that Nova preferentially regulates removal of introns harbouring (or closest to) YCAY clusters. These results define a genome-wide map relating the position of a cis-acting element to its regulation by an RNA binding protein, namely that Nova binding to YCAY clusters results in a local and asymmetric action to regulate spliceosome assembly and alternative splicing in neurons.

Suggested Citation

  • Jernej Ule & Giovanni Stefani & Aldo Mele & Matteo Ruggiu & Xuning Wang & Bahar Taneri & Terry Gaasterland & Benjamin J. Blencowe & Robert B. Darnell, 2006. "An RNA map predicting Nova-dependent splicing regulation," Nature, Nature, vol. 444(7119), pages 580-586, November.
    • Handle: RePEc:nat:nature:v:444:y:2006:i:7119:d:10.1038_nature05304
    DOI: 10.1038/nature05304
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature05304
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature05304?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Areum Han & Peter Stoilov & Anthony J Linares & Yu Zhou & Xiang-Dong Fu & Douglas L Black, 2014. "De Novo Prediction of PTBP1 Binding and Splicing Targets Reveals Unexpected Features of Its RNA Recognition and Function," PLOS Computational Biology, Public Library of Science, vol. 10(1), pages 1-18, January.
    2. Maciej Bak & Erik Nimwegen & Ian U. Kouzel & Tamer Gur & Ralf Schmidt & Mihaela Zavolan & Andreas J. Gruber, 2024. "MAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:444:y:2006:i:7119:d:10.1038_nature05304. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.