ABSTRACTS

Genome-wide association studies (GWAS) show that the genetic changes associated with chronic illnesses like Alzheimer's, diabetes, and heart disease do not lie in the protein-coding regions, but in the noncoding DNA.  Noncoding DNA contains inter alia regulatory elements, including promoters, enhancers and inhibitors or silencers of transcription and barrier insulators, some structural elements of chromosomes (including telomers and satellite DNA); repetitive sequences or transposons. Transposons reflect not only a record of crucial alterations in our DNA over millennia, but they are also mobile and move from one part of the genome to another, causing smaller or larger mutations in genes or alternatively reversing mutations.  

Instructions for the formation of various kinds of non-coding RNAs, which are involved in protein assembly, blocking the process of protein production, and regulation of gene activity in response to changes in the environment are also found in non-coding DNA.  Specialized RNA molecules, produced from noncoding DNA, include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), microRNAs (miRNAs), that block the process of protein production; and long noncoding RNAs (lncRNAs), that have diverse roles in regulating gene activity. 

Non-coding RNAs are now increasingly thought to the link between the non-coding genome and various chronic illnesses. Consistent ‘wrong’ environmental signals can lead to RNA molecules that can cause a disease state, by altering gene activity such that it results in an inflammatory response or promotes cell death. Non-coding RNAs can enhance the activity of or switch off genes that normally prevent the formation of tumours.  While the drug development industry has largely pursued proteins as drug targets, disruption of the non-coding RNAs are progressively being investigated in the field of cancer vaccines (CureVac), scar tissue formation, or fibrosis, in the heart (Haya Therapeutics). Information on noncoding gene sequences, and epigenetic programming are providing opportunities for personalized medicine as well as innovative treatments for rare and previously incurable diseases.