Shedding a new light on genetic treatments, evolution

Written by Keach Nichole F. Lotho (Riboswitch)

Researchers from the Department of Cell Biology and Molecular Genetics in the University of Maryland discovered that double-stranded RNA (dsRNA) made in the neurons of Caenorhabditis elegans, a species of roundworm commonly used in laboratory experiments, can trigger silencing of genes in the germ cells which are known to produce sperm or egg cells essential in an organism’s reproductive processes. In this particular study published on early 2015 in the online database of the Proceedings of the National Academy of Sciences, the team of scientists found out that the silencing of a gene of a matching sequence could persist in more than 25 generations.

C. elegans visualized using fluorescent dye
Photo | WormBook

The inheritance through the germline is believed not to be influenced by environmental effects which can alter the soma or body cells. However, certain genes in the germline can be silenced, or switched off, as caused by environmental factors. These modifications are sometimes transgenerational; that is, they can be passed across multiple generations. These transgenerational effects are initiated either by direct changes in the ancestral germline or by the transmission of genetic information from somatic cells to the germ cells. Researchers find it difficult to distinguish between the two aforementioned mechanisms, causing manipulation in the activity of gene in specific tissues through the use of dsRNA.

In order to come up with the recent finding that genes within the germ cells can be silenced by dsRNA, scientists used the neurons of C. elegans to produce molecules of dsRNA. Such molecules are known to travel between somatic cells and can silence genes corresponding to a particular section of a cell’s DNA. The transfer among tissues of gene-regulatory information continues through the transport of another form of dsRNA called mobile RNA. Mobile RNAs are molecules that enter the germline and give an organism the ability to transfer gene-specific regulatory information from the soma across generations, a mechanism enabling for transgenerational effects in animals.

Nerve cells (magenta) and germ cells (green) of C. elegans stained by fluorescent dyes
Photo | Sindhuja Devanapally

This finding is a major breakthrough in understanding evolutionary biology considering that some other animals may use such dsRNA transport to become accustomed to their environment. Furthermore, the study envisions its contribution to the advancement of medical treatments for genetic disorders through RNA interference (RNAi) wherein a specific gene-causing disease that matches the dsRNA can be targeted to be switched off. This, however, posts a problem as regards to the long-term stability of gene silencing. 

References 

Sindhuja Devanapally, Snusha Ravikumar, Antony M. Jose. Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing. Proceedings of the National Academy of Sciences, 2015; 201423333 DOI:10.1073/pnas.1423333112

University of Maryland. (2015, February 2). New mechanism of inheritance could advance study of evolution, disease treatment. ScienceDaily. Retrieved June 25, 2015 from www.sciencedaily.com/releases/2015/02/150202212449.htm