Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions
Ruijter, Anna Elisabeth Maria
Odom, Duncan T.
Murrell, AdeleNote: Order does not necessarily reflect citation order of authors.
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CitationStojic, L., M. Niemczyk, A. Orjalo, Y. Ito, A. E. M. Ruijter, S. Uribe-Lewis, N. Joseph, et al. 2016. “Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions.” Nature Communications 7 (1): 10406. doi:10.1038/ncomms10406. http://dx.doi.org/10.1038/ncomms10406.
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.
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