Gene that controls the birth of neurons discovered

Discovery of long non-coding RNA’s role in neurogenesis may lead to cures for diseases such as Alzheimer’s disease
August 29, 2013

Evidence that RMST is necessary for neuronal differentiation: overexpression of RMST led to a 3-fold increase in neuron-specific beta tubulin (bottom) compared to control (top). Scale bars represent 100 microns. (Credit: Shi-Yan Ng et al./Molecular Cell)

Scientists at A*STAR’s Genome Institute of Singapore (GIS) have discovered an unusual gene that controls the generation of neurons. This important finding is crucial in understanding serious diseases of the brain such as Alzheimer’s disease, the researchers say.

The central nervous system is composed of numerous cell types that develop into a complex, higher-ordered structure. The birth of neurons (neurogenesis) is a process that requires exquisite temporal and spatial control of hundreds of genes.

The expression of these genes is controlled by regulatory networks, usually involving proteins, which play critical roles in establishing and maintaining the nervous system. Problems with neurogenesis are the basis of many neurological disorders, so understanding the molecular details of neurogenesis is crucial for developing treatments of serious diseases.

RMST controls the birth of new neurons

Researchers at the GIS, led by Principal Investigator Prof Lawrence Stanton, discovered a key component within a gene regulatory network that controls the birth of new neurons, called RMST.

Surprisingly, this new discovery is not a protein. Rather, RMST is an atypical, long non-coding RNA (lncRNA for short; pronounced as “link RNA”). LncRNAs are a newly discovered class of RNA whose functions remain mostly unknown.

They found that RMST acts directly within a gene regulatory network. This sheds light on the process of neurogenesis, and also generates new insight into how lncRNA works together with protein components to regulate the important biological processes of gene expression.

“Stanton and colleagues show how RMST, a human lncRNA, directly regulates SOX2, a key transcription factor protein that is instrumental for directing the birth of new neurons,” said Associate Prof Leonard Lipovich, from the Center for Molecular Medicine and Genetics at the Wayne State University and a member of GENCODE. Even more intriguingly, they highlight that RMST controls SOX2 by directly interacting with the protein.


Researchers at Harvard University, National University of Singapore, and Nanyang Technological University were co-authors of the paper.