New research helps better understand the basic biology of nerve cells

Scientists are beginning to understand the precise workings of a type of gene that, unlike other genes, does not code for proteins – the building blocks of life.

New research from the University of Bath shows the mechanism by which genes coding for a subset of long non-coding RNAs (lncRNAs) interact with neighboring genes to regulate the development and function of essential nerve cells.

Despite their prevalence on lncRNA-coding genes in the genome (estimates range from 18,000 to 60,000 lncRNA genes in the human genome compared to 20,000 protein-coding genes), these DNA segments have already been considered undesirable precisely because the information contained within does not result in the production of a protein. However, it is now clear that some lncRNAs are anything but junk, and these could play a key role in restoring physical function in people who have suffered severe nerve damage.

Although the function of most lncRNA genes remains a mystery, a subset is co-expressed in the brain with neighboring genes that code for proteins involved in the control of gene expression. In other words, the genes for these lncRNAs and their protein-coding neighbors work in pairs. Together they regulate the development and function of essential nerve cells, particularly in the brain during embryonic development and early life.

The new study describes the regulatory pathway involved in controlling levels of one of these gene pairs. Their location and quantity in the genome must be carefully coordinated, as must the timing of their activity.

We have previously defined one of the most profound functions of lncRNA in the brain and our new study identifies an important signaling pathway that acts to coordinate the expression of this lncRNA and the key protein-coding gene with which it is associated.


Dr Keith Vance, Study Lead Author, Department of Biology and Biochemistry, University of Bath

“This new research brings us closer to understanding the basic biology of nerve cells and how they are produced. Regenerative medicine is the end game and with further research we hope to develop a deeper understanding of how lncRNA genes work in the brain.

He adds: “This knowledge could be important for scientists looking for ways to replace faulty neurons and restore nerve function – for example in people who have had strokes.”

The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and is published today in PLOS genetics.

Source:

Journal reference:

Pavlaki, I., et al. (2022) Chromatin interaction maps identify Wnt-responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells. PLOS genetics. doi.org/10.1371/journal.pgen.1010230.

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