by MM Soh
(NB: Word Vomit. Unedited Typing at 12am.)
I have always had a slight yet keen affection for what is colloquially known as “junk DNA” and “jumping DNA” or also, “non-coding DNA” and “transposons”. Now, the beauty of biology is that nothing is completely useless. There is always some function associated with the thing, or evolution would have gotten rid of it. There is no better optimiser than Nature, which had billions of years to create what is today.
Non-coding DNA, which are DNA that do not code for any proteins, often forms the vast majority of DNA in many organisms. In humans, it is about 98%. How can something present in such a great proportion not have some sort of function?
The genomic era came and went with the Human Genome Project’s start in 1990 and completion in 2003. It was a gold rush to map all the genes that could be mapped to some function in all the various types of organisms available, such as the model organisms fruit flies Drosophila, mice, zebrafish, and the nematode C elegans. Eventually what could be mapped was mapped and scientists began to turn their attention to the non-coding DNA.
Non-coding DNA is increasingly recognised to serve important functions in evolution, disease and keeping cells functioning and well. Some examples of non-coding DNA include introns, DNA that could be transcribed into special RNA such as rRNA, tRNA, miRNA and siRNA, telomeres which form at the ends of chromosomes to protect them from degradation, transposons which hop around the genome and plays an important role in evolution, pseudogenes, among others.
An elementary example of the importance of non-coding DNA would be introns. Compared to exons, which are coding regions, intronic sequences are comparatively much larger despite being commonly illustrated to be the same length or smaller — introns can be 10 times or even 50 times longer than exons.
In pre-mRNA, introns space between exons, which are coding regions, and alternative splicing, or various methods of pasting the coding regions together, can be performed, which eventually gives rise to different proteins which may serve different and even contrasting functions, adding sensitivity in regulatory control.
Some of the other more commonly established non-coding DNA include DNA which code for tRNA, or transfer RNA, and rRNA, or ribosomal RNA, which have essential roles in the translation of mature mRNA, which are sequences derived from coding DNA, into functional proteins. Some of these non-coding DNA sequences are promoters, terminators, which are important in helping cells decide when to start and stop transcribing. Telomeres, which form the ends of chromosomes and protect them from degradation, become shorter and shorter as the cells divide. This allows cells to time themselves and reach senescence, also known as programmed cell death, at an appropriate juncture before they get old and start accumulating harmful mutations. In cancer cells, telomerase, an enzyme that allows telomeres to be maintained, is often expressed which allows cancer cells to attain some sort of immortality and continue dividing non-stop, which can cause tumours to form and overwhelm the system.
More recently, over the last two decades, interest in other types of RNA, such as siRNA, or silencing RNA, and miRNA, also known as microRNA has led to an explosion in knowledge in this area. Increasingly these RNA are shown to have subtle influences over the regulatory control within the cells, for example in activation, inhibition, silencing, degradation and modification of transcripts…. and even each other. A large combination of all these non-coding RNA can have huge impacts on the regulation of cell function. They can also help us identify when we have diseases. For example it is known that miRNA expression is dysregulated in cancer, such as miR-486, which is known to be significantly downregulated in certain types of lung cancer, and affect cell properties like proliferation and migration. Money has been dumped into identifying non-coding RNA such as miRNA in exosomes, which are basically secretions of cells that can contain various many things such as various kinds of proteins, and RNA, and use that to identify and differentiate samples which are cancerous and which are not, opening up avenues for diagnosis among others.
M. Mitchell Waldrop — ‘Everything affects everything else, and you have to understand that whole web of connections.’
