Inhibition of transcriptional interference with siRNA. The top panel depicts how GNG12-AS1 modulates the expression of the active DIRAS3 allele through transcriptional interference. GNG12-AS1 may act as a rheostat for DIRAS3 transcription rate. The lower panel depicts how exogenous siRNA molecules in a complex with AGO2 can bind to both the TSS and GNG12-AS1 to inhibit Pol II, and block further transcription initiation and elongation of GNG12-AS1. As a result of transcriptional silencing of GNG12-AS1, transcriptional interference is reduced leading to increased transcription of DIRAS3.
Supposed non-coding DNA, found in between genes, plays a role in suppressing cancer, according to new research by Universities of Bath and Cambridge. The human genome contains about 3m of DNA, of which only 2% has genes that code for proteins. Since the sequencing of the complete human genome in 2000, scientists have puzzled over the role of the remaining 98%. In recent years it has become apparent that a lot of this “junk” DNA is actually transcribed into non-coding RNA. The discovery may help develop new treatments for cancer.
Dr Adele Murrell explained: “The number of cells in our body are balanced by the level at which cells replicate and replace the ones that die. Sometimes the switches that control this growth get stuck in the ‘on’ position, which can lead to cancer” and metastases. “In our study we’ve identified that GNG12-AS1, a strand of non-coding RNA, prevents the growth switch getting stuck and suppresses metastasis. The specific genomic region where this non-coding RNA is located often gets damaged in breast cancer patients – this control is removed and the cancer cells spread.”
The research team found that this non-coding RNA fragment maintains healthy cells through 2 mechanisms:
1. by regulating levels of DIRAS3, one of its neigboring genes that is involved in cell replication
2. by suppressing a network of genes that prepare cells to change their shape and prepare for metastasis.
The team were able to distinguish between these two mechanisms by using smaller interfering RNAs (siRNAs) to either specifically stop the non-coding RNA from being made, or to degrade the RNA immediately after it was made. Both approaches led to cells changing their shape and transforming into migratory cells. However, only the first approach affected DIRAS3 and the cell cycle.
The team anticipates their findings could be used understand how other non-coding RNAs function and to develop potential gene therapies to treat cancer. Dr Kat Arney said: “Only a tiny fraction of our DNA contains actual genes, and we know that at least some of the bits in between — often dismissed as ‘junk’ — play important roles in controlling how genes get switched on and off at the right time and in the right place. http://www.bath.ac.uk/research/news/2016/02/01/junk-dna-prevents-cancer/ http://www.nature.com/ncomms/2016/160202/ncomms10406/full/ncomms10406.html
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