First we learned that DNA is transribed into RNA (via a process called transcription) and that RNA is translated into protein (via a process called translation). Then we discovered that RNA transcribed from the DNA (gene) comprises both coding regions (exons) and intervening sequences (introns) –– and that the exons are linked together to form the messenger RNA (mRNA). Then, it was concluded that, because the exons only comprised 1.5% of the total genome, the rest must be called “junk” DNA. Then the significance of promoter regions (outside the exons) was realized, and DNA segments (usually) upstream from the gene’s promoter were full of important enhancer modules that controlled regulation and expression. Then many kinds of small micro RNAs (miRNAs) were discovered, which were not translated into protein, but could control a gene’s expression by binding (tying up) many mRNAs so that the mRNAs were unable to be translated into protein.
Finally, thousands of long noncoding RNAs (lncRNAs) –– from 100 to 100,000 nucleotides in length –– have been discovered, again not being translated into protein. They are involved frequently with precise regulation (of gene expression, developmental expression), but at the present time, most have unknown functions.
In the attached publication (and editorial), a brand new (mind-blowing) function has been discovered. Authors demonstrate that lncRNAs guide the animal’s DNA damage response. DNA damage activates transcription of the DINO lncRNA (Damage-Induced NOncoding) lncRNA, by way of TP53. DINO was required for TP53-dependent gene expression, cell-cycle arrest, and programmed cell death (apoptosis) in response to DNA damage. DINO expression was sufficient even to activate damage-signaling and cell cycle arrest in the absence of DNA damage. DINO binds to the TP53 protein and stimulates its stabilization –– mediating a TP53 auto-amplification loop. Mouse Dino knockout, or promoter inactivation, dampens TP53-signaling and ameliorates acute radiation syndrome in vivo. Therefore, here is an example of an inducible lncRNA that can create a feedback loop with its c
Nat Genet Nov 2o16; 48: 1370–1376 [article] plus pp 1298–1299 [News-N-Views editorial]