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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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. 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.
LanguageEnglish
Article number10406
JournalNature Communications
Volume7
DOIs
StatusPublished - 2 Feb 2016

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Long Noncoding RNA
Small Interfering RNA
interference
suppressors
dissection
gene expression
Transcription
products
progressions
tumors
Dissection
cycles
RNA Polymerase II
causes
cells
Gene expression
Cell Movement
Tumors
Exons
Cell Cycle

Cite this

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

In: Nature Communications, Vol. 7, 10406, 02.02.2016.

Research output: Contribution to journalArticle

Stojic, L, Niemczyk, M, Orjalo, A, Ito, Y, Ruijter, AEM, Uribe-Lewis, S, Joseph, N, Weston, S, Menon, S, Odom, DT, Rinn, J, Gergely, F & Murrell, A 2016, 'Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions: 2 ', Nature Communications, vol. 7, 10406. https://doi.org/10.1038/ncomms10406
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. / Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions : 2 . In: Nature Communications. 2016 ; Vol. 7.
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