Junk DNA: Is Preventing Breast Cancer a Function?
Evolution News & Views February 6, 2016 4:33 AM
Each time a function is found for a piece of non-coding DNA, the "junk DNA" myth gets more mythological. Here's a function that has been revealed for a certain long, non-coding transcript of DNA into RNA (lncRNA). It helps prevent breast cancer and ovarian cancer.
Researchers at the University of Bath explain why it is difficult to find these functions for non-coding parts of the genome:
The human genome contains around three metres of DNA, of which only about two per cent contains 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 per cent.
In recent years it has become apparent that a lot of this non-coding DNA is actually transcribed into non-coding RNA. However, there is still a debate as to whether non-coding RNA is just 'noise' or whether it serves any function in the cell.
Part of the reason for this uncertainty is that it is very difficult to knock-out non-coding RNA without damaging the DNA, which can lead to off-target effects and false results.
They are clearly aware of the "debate" about junk DNA and the results of ENCODE that found that the majority of the genome is actually transcribed (they referenced ENCODE in the paper). As we have reported often, some members of the evolution side of the debate expect most of the DNA is junk. The design side expects that much of it (but not necessarily all) is functional. Thanks to this research, we have a new case that may point the way to future discoveries.
The news release is titled, "'Junk' DNA plays role in preventing breast cancer." It's based on an open-access paper in Nature Communications. Most readers scanning the paper will see what researchers are up against. Discussion of the complex interactions of parts -- lncRNAs transcripts, small interfering RNAs (siRNAs), promoters, exons, introns, alleles, interference in cis and trans and all the rest -- gets into the technical weeds fast. Thankfully, the release simplifies the essence of the finding. Basically, a piece of non-coding DNA "keeps cells healthy" by preventing a genetic "switch" from getting stuck.
Dr Adele Murrell, from the University of Bath's Department of Biology & Biochemistry, led the study. She 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.
"As the tumour grows and the cancer cells get crowded, they start to break away from the tumour, change shape and are able to burrow through tissues to the bloodstream where they migrate to other parts of the body, which is how the cancer spreads. This process is called metastasis and requires a whole network of genes to regulate the transformation of cell shape and mobilisation.
Dr Lovorka Stojic, from Cancer Research UK Cambridge Institute, the first author of this work 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 researchers found that the lncRNA GNG12-AS1 acts as a molecular "rheostat" (their term) that controls the expression of an adjacent gene, DIRAS3, a tumor suppressor. It does it by two mechanisms. One is by regulating the number of transcripts of the tumor suppressor. But if that gets out of control, it can even suppress the "network of genes that prepare cells to change their shape and prepare for metastasis."
By experimentally reducing the amount of GNG12-AS1 produced, either by preventing its transcription or destroying the transcripts, they found that cells start becoming cancerous. This explains why in cancer patients, the switch is stuck:
DIRAS3 is downregulated in 70% of breast and ovarian cancer, and its loss of expression correlates with cancer progression and metastasis. The mechanism responsible for DIRAS3 downregulation to date involves different epigenetic mechanisms and loss of heterozygosity. We hypothesized that TI [transcriptional interference] by GNG12-AS1 could represent an additional layer of regulating DIRAS3 dosage.
The interactions are far more complex than can be described here. Suffice it to say that this long non-coding RNA, which would have been considered "junk" previously, plays a crucial role in regulating the amount of an important tumor suppressor gene. It's a "stable lncRNA localized in the nucleus" with a half-life of 20 to 25 hours, meaning it needs to be transcribed often. Other processes regulate the amount of the lncRNA in a very complex choreography of enhancers, suppressors, and feedback loops. Levels of expression also vary depending on the tissue involved.
It has become increasingly clear that non-coding parts of the genome play vital roles in regulating the coding parts. Regulation is an important function. A system that generates parts without regard to the amount needed is a system out of control. How cool is it to find a code that codes for products that regulate the amount of products in other parts of the code? Not only do we see function emerging for the non-coding regions, we see design on a more colossal scale than anyone could have imagined.
The University of Bath is an internationally recognized center of excellence in biological research. It's encouraging to see their biologists actively challenging the "junk DNA" myth:
Dr Kat Arney, science communication manager at Cancer Research UK, 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.
When the Human Genome project found that only 2 percent of the genome coded for proteins, the right question should have been, "What is all the rest doing?" Some evolutionists were too quick to dismiss it as a pile of useless leftovers from time and chance. Cancer patients around the world can be grateful that these researchers didn't buy that explanation, but looked beyond the unknown for greater understanding.
"Research like this is helping is to unpick the precise details about how these regions work, shedding light on their potential role in the development [or prevention] of cancer and pointing towards new approaches for tackling the disease."
If a system works, it's not happening by accident. That's the intelligent-design spirit that promises to shed more light into the genomic black box.
Evolution News & Views February 6, 2016 4:33 AM
Each time a function is found for a piece of non-coding DNA, the "junk DNA" myth gets more mythological. Here's a function that has been revealed for a certain long, non-coding transcript of DNA into RNA (lncRNA). It helps prevent breast cancer and ovarian cancer.
Researchers at the University of Bath explain why it is difficult to find these functions for non-coding parts of the genome:
The human genome contains around three metres of DNA, of which only about two per cent contains 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 per cent.
In recent years it has become apparent that a lot of this non-coding DNA is actually transcribed into non-coding RNA. However, there is still a debate as to whether non-coding RNA is just 'noise' or whether it serves any function in the cell.
Part of the reason for this uncertainty is that it is very difficult to knock-out non-coding RNA without damaging the DNA, which can lead to off-target effects and false results.
They are clearly aware of the "debate" about junk DNA and the results of ENCODE that found that the majority of the genome is actually transcribed (they referenced ENCODE in the paper). As we have reported often, some members of the evolution side of the debate expect most of the DNA is junk. The design side expects that much of it (but not necessarily all) is functional. Thanks to this research, we have a new case that may point the way to future discoveries.
The news release is titled, "'Junk' DNA plays role in preventing breast cancer." It's based on an open-access paper in Nature Communications. Most readers scanning the paper will see what researchers are up against. Discussion of the complex interactions of parts -- lncRNAs transcripts, small interfering RNAs (siRNAs), promoters, exons, introns, alleles, interference in cis and trans and all the rest -- gets into the technical weeds fast. Thankfully, the release simplifies the essence of the finding. Basically, a piece of non-coding DNA "keeps cells healthy" by preventing a genetic "switch" from getting stuck.
Dr Adele Murrell, from the University of Bath's Department of Biology & Biochemistry, led the study. She 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.
"As the tumour grows and the cancer cells get crowded, they start to break away from the tumour, change shape and are able to burrow through tissues to the bloodstream where they migrate to other parts of the body, which is how the cancer spreads. This process is called metastasis and requires a whole network of genes to regulate the transformation of cell shape and mobilisation.
Dr Lovorka Stojic, from Cancer Research UK Cambridge Institute, the first author of this work 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 researchers found that the lncRNA GNG12-AS1 acts as a molecular "rheostat" (their term) that controls the expression of an adjacent gene, DIRAS3, a tumor suppressor. It does it by two mechanisms. One is by regulating the number of transcripts of the tumor suppressor. But if that gets out of control, it can even suppress the "network of genes that prepare cells to change their shape and prepare for metastasis."
By experimentally reducing the amount of GNG12-AS1 produced, either by preventing its transcription or destroying the transcripts, they found that cells start becoming cancerous. This explains why in cancer patients, the switch is stuck:
DIRAS3 is downregulated in 70% of breast and ovarian cancer, and its loss of expression correlates with cancer progression and metastasis. The mechanism responsible for DIRAS3 downregulation to date involves different epigenetic mechanisms and loss of heterozygosity. We hypothesized that TI [transcriptional interference] by GNG12-AS1 could represent an additional layer of regulating DIRAS3 dosage.
The interactions are far more complex than can be described here. Suffice it to say that this long non-coding RNA, which would have been considered "junk" previously, plays a crucial role in regulating the amount of an important tumor suppressor gene. It's a "stable lncRNA localized in the nucleus" with a half-life of 20 to 25 hours, meaning it needs to be transcribed often. Other processes regulate the amount of the lncRNA in a very complex choreography of enhancers, suppressors, and feedback loops. Levels of expression also vary depending on the tissue involved.
It has become increasingly clear that non-coding parts of the genome play vital roles in regulating the coding parts. Regulation is an important function. A system that generates parts without regard to the amount needed is a system out of control. How cool is it to find a code that codes for products that regulate the amount of products in other parts of the code? Not only do we see function emerging for the non-coding regions, we see design on a more colossal scale than anyone could have imagined.
The University of Bath is an internationally recognized center of excellence in biological research. It's encouraging to see their biologists actively challenging the "junk DNA" myth:
Dr Kat Arney, science communication manager at Cancer Research UK, 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.
When the Human Genome project found that only 2 percent of the genome coded for proteins, the right question should have been, "What is all the rest doing?" Some evolutionists were too quick to dismiss it as a pile of useless leftovers from time and chance. Cancer patients around the world can be grateful that these researchers didn't buy that explanation, but looked beyond the unknown for greater understanding.
"Research like this is helping is to unpick the precise details about how these regions work, shedding light on their potential role in the development [or prevention] of cancer and pointing towards new approaches for tackling the disease."
If a system works, it's not happening by accident. That's the intelligent-design spirit that promises to shed more light into the genomic black box.
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