The scientists at Centre for Cellular and Molecular Biology (CCMB), Hyderabad, have demonstrated that gene silencing is achieved by small interfering RNA (RNAi) at specific loci during the conversion of euchromatin to heterochromatin. They have also demonstrated that disruption of RNAi interference mechanism in the living cell, eventually leads to disruption of specific chromosome regions.
Regulation of gene activity is controlled by several mechanisms in the cell. When the gene expression is completely stopped, or reduced dramatically, the phenomenon is known as gene silencing. One of the ways by which genes are silenced in plants and animals is by interfering with the activity of the gene through RNA, a relatively small molecule, and the process is known as RNA interference. These small 21-25 nucleotide fragments called SiRNAs are also found to degrade the mRNA, which carries information for making proteins.
In transgenic plants and animals, multiple copies of transgenes introduced into host genome, becomes inactive due to such interactions, simultaneously, even some of the host genes get silenced. This creates a major obstacle for biotechnologists who are engaged in creating transgenic organisms with new traits for crop improvements and animal husbandry or doctors who look forward to use gene therapy for treating diseases. Dr Utpal Bhadra, Dr Manika Pal Bhadra and other team members at CCMB have found a way to overcome this obstacle.
RNA -intervention, one of the very important mechanisms of gene regulation was discovered about six years ago by Dr Bhadra's team and Prof James A Birchler. Since then, RNA-intervention is being discovered and studied in many biological systems. However, it is for the first time that the CCMB team has provided evidence for the role of RNAi in gene silencing observed during the conversion of euchromatin to heterochromatin and its maintenance.
Dr Lalji Singh, director, CCMB said that the importance of RNAi in antiviral therapy and drug validation has already been illustrated. Diseases coupled with cell division and cell proliferation, such as various types of cancers, appear to be controlled by heterochromatin formation and its functioning. Understanding the role of RNAi -intervention in these processes, thus, might lead to use RNAi as a possible therapy for cancers and other related diseases, which involve cell cycle controls.
Dr Manika said that gene silencing can be vital in gene therapy, modern biology, knowing the function of unknown gene, drug development, and developing viral resistant vaccines.
Meanwhile, in a unique collaborative effort CCMB and Directorate of Rice Research, Hyderabad have developed a disease (bacterial leaf blight) resistant - Samba Masuri and Triguna rice lines through the application of molecular breeding, a DNA marker technology.