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dc.contributor.authorStojic, Lovorkaen
dc.contributor.authorNiemczyk, Malwinaen
dc.contributor.authorOrjalo, Arturoen
dc.contributor.authorIto, Yokoen
dc.contributor.authorRuijter, Anna Elisabeth Mariaen
dc.contributor.authorUribe-Lewis, Santiagoen
dc.contributor.authorJoseph, Nimeshen
dc.contributor.authorWeston, Stephenen
dc.contributor.authorMenon, Surajen
dc.contributor.authorOdom, Duncanen
dc.contributor.authorRinn, Johnen
dc.contributor.authorGergely, Fannien
dc.contributor.authorMurrell, Adeleen
dc.identifier.citationStojic et al. Nature Communications (2016) Vol. 7, Article 10406. doi:10.1038/ncomms10406en
dc.description.abstractLong 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.
dc.description.sponsorshipThe authors acknowledge all the members of Murrell, Rinn, Odom and Gergely laboratory as well as Massimiliano di Pietro, Klaas Mulder, Anna Git, Jason Carroll in Cambridge and Laurence Hurst (University of Bath) for reading and providing helpful comments on the manuscript. We also thank the Genomics, Microscopy and Bioinformatics core facilities at the Cambridge Institute for support, Christina Ernst for thumbnail image design, Ezgi Hacisuleyman for the design of the negative control vector, Cole Trapnell and David Hendrickson for providing us with lincExpress vector, Arjun Raj with the RNA FISH and Alaisdair Russell with the lentiviral work. This research was supported by The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. The authors have no conflicting financial interests.
dc.publisherNature Publishing Group
dc.rightsAttribution 2.0 UK: England & Wales
dc.subjectlong noncoding RNAen
dc.subjecttranscriptional interferenceen
dc.subjectgene regulationen
dc.titleTranscriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functionsen
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via
prism.publicationNameNature Communicationsen
dc.contributor.orcidOdom, Duncan [0000-0001-6201-5599]
dc.contributor.orcidGergely, Fanni [0000-0002-2441-8095]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idEuropean Research Council (615584)
cam.orpheus.successThu Jan 30 12:55:33 GMT 2020 - The item has an open VoR version.*

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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales