RNA interference

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RNA interference is an evolutionary mechanism found in many organisms which degrades foreign double stranded RNA molecules (dsRNA) and controls gene expression through gene silencing. Genetic studies of Caenorhabditis elegans, plants, and Drosophila have provided more evidence of this mechanism. Gene silencing occurs due to small RNA molecules being present when the mRNA is being translated by the ribosome[1]. This is called RNA interference and can be split into three steps: the initiator, the effector, and the amplification step.

The Initiator step: The presence of double-stranded RNA molecules (dsRNAs) and microRNAs (miRNAs) induces a protein called the Dicer protein. This protein cleaves the dsRNA into small interfering RNAs (siRNAs). siRNAs are approximately 22 nucleotides long and can occur naturally or be induced experimentally.

The Effector step: The siRNAs then bind to a different protein called the Argonaut protein and are cleaved into single strands. One strand of the siRNA is selected and remains bound to the Argonaute protein. This is known as the guide strand. The other strand is degraded. The combination of the Argonaut protein, the guide strand, and other proteins is called the RNA-induced silencing complex (RISC). The guide siRNA strand directs the RISC to bind to a specific target site on the mRNA being translated. The target site and the guide strand are complementary to each other. The RISC then cleaves the mRNA target site it binds to and rapidly degrades it, consequently silencing the specific gene.

The Amplification step (systematic silencing): The mechanism can be further amplified by silencing the specific gene in all the cells of the organism. This occurs by transferring siRNA fragments through transmembrane proteins into every cell. For example, if a few plant cells become infected with a virus, RNA interference can silence the foreign gene in the virus, making the plant cells resistant to the virus. Through the amplification step, the whole plant can then become resistant to the virus.

Recently, Professor Craig Hunter and colleagues at Harvard University identified the sid-1 gene. This gene encodes for a transmembrane protein that allows siRNA's to enter the cell. Therefore, sid-1 plays an important role in inducing systematic gene silencing in the whole organism. It has also been discovered that the sid-1 gene is not present in Drosophila but is present in mammals, therefore, Drosophila does not exhibit a systematic transmission of gene silencing[2].

References

  1. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of The Cell. 5th ed, New York: Garland Science. 2008.
  2. Hannon GJ. RNA interference. Nature 2002; 418: 244-251.
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