Out of sight, out of mind

By | Science & Technology
Computer generated image of neurons. Credit@juliedn

Researchers in the US have discovered that a particular RNA molecule may be directed to increase the production of neurons. The gene is called Pnky and appears to have a role in the production of neurons from neural stem cells. “Pnky is encoded near a gene called Brain, so it sort of suggested itself to the students in my laboratory,” explained assistant professor of neurological surgery and director of restorative surgery at UCSF Daniel Lim. The study was published in Cell Stem Cell late last week.

Found only in the brain, Pnky is reportedly one of the few known types of long non-coding RNA (lncRNA) molecules. lncRNAs are stretches of RNA found in the genome, they are non-protein-coding and are 200 or more nucleotides long. The team found that when Pnky was ‘knocked down’ (removed, essentially) in neural stem cells, the production of neurons increased 3- to 4-fold.

Dr. Lim commented that, “It is remarkable that when you take Pnky away, the stem cells produce many more neurons. These findings suggest that Pnky, and perhaps lncRNAs in general, could eventually have important applications in regenerative medicine and cancer treatment.”

Using mass spectrometry, Dr. Ramos found that Pnky binds a protein called PTBP1, which is also found in brain tumours. Pnky and PTBP1 appear to function together in neural stem cells to suppress the production of neurons and therefore tumour growth.

Genes code for proteins, however fewer than 2% of the entire human genome encodes proteins – a similar number to the nematode worm, C. elegans. However, more than 90% (some experts believe all) of the genome is expressed, producing many non-coding RNA molecules. It is becoming increasingly clear that lncRNAs are more than just ‘transcriptional noise’ even though they are one of the least understood species of genomic material.

Initially when the human genome was first sequenced in 2000, the remaining 98% of the genome was considered ‘junk DNA’, deterring scientists from investigating the ‘dark matter’. However, the ‘junk’s’ persistence in the genome led to one of genetics’ most important discussions – how much of the genome is functional? The functionality of lncRNAs has been examined by a number recent evolutionary research projects. Studies such as this one led by Dr. Lim, also demonstrate how non-coding regions of the genome, such as Pnky, might have profound effects, with applications in regenerative medicine, including the treatment of conditions such as Alzheimer’s and Parkinson’s.

Neurons expressing green fluorescent protein. Credit@GerryShaw

Neurons expressing green fluorescent protein. Credit@GerryShaw

Driven by paradigm shifts in the understanding of genomic architecture, lncRNAs are being characterised at a rapid pace. They are thought to play an important role in embryonic development and cancer. In fact, underlying most cellular processes are complex gene regulatory networks. Often, two genetically identical cells in the same environment may show significant variations in their gene expression as a result of lncRNA interactions.

A more holistic approach to the genome’s mysterious side has made discoveries like this one possible. “It is possible that not all lncRNAs have important biological functions, but we are making a start toward learning which ones do, and if so, how they function. It’s a new world of experimental biology, and the students in my lab are right there on the frontier,” said Lim. This study adds to the growing store of knowledge around lncRNAs and may prove how genomic ‘dark matter’ is possibly why humans are the talking, empire-building, socially complex organisms they are. lncRNAs keep the body healthy and are also accountable when things go awry. Lim’s research may help make the personalised medicine of neurological conditions a reality, matching patients’ unique conditions to the best care for them.

In what ways might the ‘dark matter’ of the human genome productively contribute to bodily processes?


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