Junk DNA: goodbye!: lncRNA controls breast cancer (Introduction)

by David Turell , Thursday, February 11, 2016, 01:13 (3209 days ago) @ David Turell

More so called junk DNA is now seen functional:-http://www.evolutionnews.org/2016/02/junk_dna_is_pre102591.html-"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.-***-"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." -My usual comment: How much complexity has to be found before design is accepted?