Epigenetics – beyond genes
Box 1 | RNA interference and epigenetics
RNA interference is a natural defence mechanism to control levels of gene activity where small segments of RNA cause messenger RNA to be degraded before it is translated into protein.
RNA as a regulator of gene activity
The discovery of RNA interference began in plants, when researchers tried to engineer petunia plants to produce more coloured pigment in flowers, by adding extra copies of a gene responsible for pigment formation. Instead of an increased amount of pigment, they found that many of the flowers lacked pigment. The extra copies of the gene were somehow suppressing the activity of the original gene. Later, researchers discovered that small RNAs were present in suppressed plants, but absent in non-silenced plants.
Continued research revealed an entirely new way of regulating gene activity that involved small RNAs.
Types of small RNAs
Small segments of RNA generally come in two varieties: small interfering RNAs from invading viruses and microRNAs that are encoded by genes in the cell. As research continues, new types of small interfering RNAs are being identified, particularly in plants.
Small interfering RNAs
Unlike DNA, RNA normally exists only in the single-stranded form in a cell. Because the genetic material of some viruses is made from double-stranded RNA, cells treat the presence of double stranded RNA as a sign of infection by a virus.
When double-stranded RNA is found in the cell, it is chopped into short sequences of between 21 to 24 bases in length, and is then used as a guide to find and destroy single-stranded messenger RNA with the same sequence of bases. This mechanism helps prevent the invading virus from using the cell’s machinery to reproduce.
Researchers can ‘trick’ the cell into destroying the messenger RNA from one of its own genes by deliberately introducing double-stranded RNA with the same nucleotide sequence as a gene to be silenced. Because the messenger RNA is destroyed before it can be translated into a protein, the normal appearance or function of the cell is changed.
Small interfering RNAs and methylation of DNA in plants
In plants, small interfering RNAs can also trigger the methylation of DNA. Small RNAs that are similar in sequence to a region of DNA, cause the DNA to be methylated. The details of the mechanism are not yet fully understood, but it represents yet another way to control the level of gene activity.
MicroRNAs
Thousands of microRNAs have been identified in many species, including humans, but their role in the cell was a mystery until recently.
MicroRNAs are regulators of embryo development, cell replication, plant development and stress responses. Because they are involved in timing of cell development and metabolism, any change to them can trigger cancer. Researchers have discovered that cancer cells contain less microRNA than healthy cells, and each type of cancer has its own distinctive microRNA fingerprint. MicroRNAs are also known to regulate the expression of c-Myc, an oncogene that is implicated in 15 per cent of human cancers.
The discovery of microRNA and its role in development has led to a new appreciation of parts of the genome that were once considered ‘junk DNA’.
Boxes
Box 2. RNA interference and plant technology
Box 3. The Human Epigenome Project
Related sites
Flash animation: Mechanism of RNA interference (Nature Reviews Genetics, UK)
RNA interference and gene silencing: History and overview (Ambion, USA)
RNAi (NOVA scienceNOW, Public Broadcasting Station, USA)
Page updated October 2006.