IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10406.html
   My bibliography  Save this article

Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions

Author

Listed:
  • Lovorka Stojic

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Malwina Niemczyk

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Arturo Orjalo

    (Biosearch Technologies Inc.
    Present address: Genentech, Inc.1 DNA Way, South San Francisco, California 94080, USA.)

  • Yoko Ito

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Anna Elisabeth Maria Ruijter

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Santiago Uribe-Lewis

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Nimesh Joseph

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Stephen Weston

    (Centre for Regenerative Medicine, University of Bath, Claverton Down)

  • Suraj Menon

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Duncan T. Odom

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • John Rinn

    (Harvard University)

  • Fanni Gergely

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way)

  • Adele Murrell

    (Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way
    Centre for Regenerative Medicine, University of Bath, Claverton Down)

Abstract

Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1, a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12-AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding. Transcriptional, but not post-transcriptional, silencing of GNG12-AS1 causes concomitant upregulation of DIRAS3, indicating a function in transcriptional interference. This change in DIRAS3 expression is sufficient to impair cell cycle progression. In addition, the reduction in GNG12-AS1 transcripts alters MET signalling and cell migration, but these are independent of DIRAS3. Thus, differential siRNA targeting of a lncRNA allows dissection of the functions related to the process and products of its transcription.

Suggested Citation

  • Lovorka Stojic & Malwina Niemczyk & Arturo Orjalo & Yoko Ito & Anna Elisabeth Maria Ruijter & Santiago Uribe-Lewis & Nimesh Joseph & Stephen Weston & Suraj Menon & Duncan T. Odom & John Rinn & Fanni G, 2016. "Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10406
    DOI: 10.1038/ncomms10406
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10406
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10406?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
    ---><---

    Citations

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


    Cited by:

    1. Charles Limouse & Owen K. Smith & David Jukam & Kelsey A. Fryer & William J. Greenleaf & Aaron F. Straight, 2023. "Global mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions," Nature Communications, Nature, vol. 14(1), pages 1-21, 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:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10406. 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.