Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions
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Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions
| Title: | Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions |
| Author: |
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
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Stojic, 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. |
| Full Text & Related Files: |
4740813.pdf (1.755Mb; PDF) 
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| 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. |
| Published Version: | doi:10.1038/ncomms10406 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740813/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318707 |
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