Although the function of most long noncoding RNA (lncRNA) genes remains a mystery, a subset is co-expressed in the brain along with neighboring genes that code for proteins involved in gene expression control. Now, a new study by scientists at the University of Bath demonstrates the mechanism by which genes coding for a subset of IncRNA interact with neighboring genes to regulate the development and function of essential nerve cells.

Their findings are published in the journal PLOS Genetics in an article titled, “Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells.”

“Central nervous system-expressed lncRNAs are often located in the genome close to protein-coding genes involved in transcriptional control,” wrote the researchers. “Such lncRNA-protein coding gene pairs are frequently temporally and spatially co-expressed in the nervous system and are predicted to act together to regulate neuronal development and function. Although some of these lncRNAs also bind and modulate the activity of the encoded transcription factors, the regulatory mechanisms controlling co-expression of neighboring lncRNA-protein coding genes remain unclear. Here, we used high-resolution NG Capture-C to map the cis-regulatory interaction landscape of the key neuro-developmental Paupar-Pax6 lncRNA-mRNA locus.”

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

“We previously defined one of the most profound functions for 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 that it is paired with,” explained Keith Vance, PhD, lead author of the study from the department of biology & biochemistry at the University of Bath.

“This new research takes 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 operate in the brain.”

He added: “This knowledge could be important for scientists looking for ways to replace defective neurons and restore nerve function—for instance in people who have had strokes.”

Their study provides new insights into the chromatin interactions, transcription factors, and signaling pathways controlling Paupar-Pax6 co-expression in the neuronal lineage and has general importance for understanding the wider role of lncRNA-mRNA transcription units in neuronal commitment, differentiation, and function.

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