Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions: 2 

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 Gergely, Adele Murrell

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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. Additionally, the reduction in GNG12-AS1 transcripts alters MET signaling 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.
Original languageEnglish
Article number10406
JournalNature Communications
Publication statusPublished - 2 Feb 2016

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