Major Implications of RNA Silencing…Why is it important?

First, found in tobacco plants as a viral defense role against the ringspot virus, which presents the first role of RNA silencing.  As seen in the infected tobacco plant, the ringspot virus on the lower leaves activates the viral RNA silencing to inhibit the virus from spreading to the upper leaves.  Another role of RNA silencing in plants includes the protection of the genome from the damage that could be done by DNA methylation of certain nucleotide sequences, which is guided by transgene and viral RNAs.  Although the viral RNA has its own defense against the RNA silencing mechanisms, which are primarily enforced through suppressor proteins that are part of the genome of the particular virus, and have enough of a structure difference, through evolution, that they do not have a common sequence associated with them.  The secondary mechanism, by which they defend themselves, is thought to be through a compartmentalized structure that allows for the RNA to be hidden from the silencing mechanisms.  Not only can the cells have a silencing role against the virus, but the virus itself can induce the silencing and suppress the cell itself, which can be the cause of the symptoms that the plant exhibits.  The feedback mechanism is also used in plants to regulate the amount of mRNAs being made depending on the amount of silencing miRNAs present in the cell.  One specific example of this is gibberellic acid (GA), which, when stimulated, increases MYB33 that initiates flowering, and also produces in increases in miR159.  miR159 then acts on the increase in MYB33 to decrease the production of GA, as seen in Figure 1.

 

                                                Figure 1 – Diagram of feedback RNA silencing plants

(RNA silencing in plants, David Baulcombe NATURE | VOL 431 | 16 SEPTEMBER 2004 | http://www.nature.com/nature)

The viral defense role is not confined to plants, but is found in a variety of eukaryotic organisms.  Being the most common role of RNA silencing in animals, the overarching goal is to protect the genetic code from damage and mutation.  In an effort to distinguish between the “good” mRNAs and the “bad” mRNAs, all of the “good” mRNAs have a similar structure that is characteristic to that person.  The “bad” mRNAs are targeted by siRNAs, cut portions (by the Dicer enzyme) of dsRNA, through the base pair interactions, which allow other enzymes to come in and cut the mRNA into pieces.  This provides amplification of the response to a particular set of “bad” mRNAs, which is again amplified by the catalytic mechanism that allows each of the siRNAs to be used multiple times.  When there are no more mRNAs to be base paired to, the siRNAs are no longer made since they are not stable when by themselves for very long.  The role of RNA silencing in animals still has a lot that needs to be worked on. 

(RNA Silencing: The Genome’s Immune System, Ronald H. A. Plasterk, http://www.sciencemag.org SCIENCE VOL 296 17 MAY 2002)

The following video shows the processes in pictoral format in even more detail: