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

Authors :
Stojic, Lovorka
Niemczyk, Malwina
Orjalo, Arturo
Ito, Yoko
Ruijter, Anna Elisabeth Maria
Uribe-Lewis, Santiago
Joseph, Nimesh
Weston, Stephen
Menon, Suraj
Odom, Duncan T.
Rinn, John
Gergely, Fanni
Murrell, Adele
Odom, Duncan T [0000-0001-6201-5599]
Apollo - University of Cambridge Repository
Source :
Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016), Nature Communications
Publication Year :
2016
Publisher :
Nature Portfolio, 2016.

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.<br />LncRNAs regulate gene expression via their RNA product and through transcriptional interference. Here, Stojic et al. uncouple these functions by using multiple siRNAs against GNG12-AS1 to show that this lncRNA has a product related role in MET signaling while its transcription modulates DIRAS3 expression.

Details

Language :
English
ISSN :
20411723
Volume :
7
Issue :
1
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.pmid.dedup....d01c8d2387bcd8129c2d0b3d483dc261