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RNA interference.

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( I've edited the post on RNA interference, making it much more complete).

L '

RNA interference (RNA interference) was discovered for the first time in a nematode worm (Caenorhabditis elegans



). It was observed that the double-stranded RNA (dsRNA
, double stranded RNA
) caused gene silencing in a sequence-specific. Researchers had long thought that the RNA would be a perfect tool for the control of gene expression, since the right sequence of RNA should bind DNA and interfere with its transcription. While studying the efficiency of antisense RNA as a suppressor of gene expression, it was found that dsRNA was more efficient to turn off the transcription of a gene.

In our cells the presence of double-stranded RNA can be a big problem. Although cells are present in the transfer RNA
and ribosomes, which contain some sharp edges hairpin and then double helix, most of our RNA, and especially the messenger RNA is a single chain. Many viruses, however, form long stretches of double-stranded RNA as their genome doubling. If our cells are double-stranded RNA, interpret it as having a viral infection and produce a response that often leads to death of the entire cell. The plants and animals, however, has other defenses targeted directly attack viral RNA, called RNA interference

.

Since its discovery it has been observed that the mechanism of RNA interference was also present in plant cells, in which is a way to degrade the viral RNA. its function as a result was also observed in Drosophila and mammals. At present it is believed that RNAi is a natural regulatory mechanism that controls gene expression. It could also be a protection mechanism against harmful gene products oncogenes that summarize too much.

produce interference

as shown at the top of RNA interference begins when you submit a long chain of double-stranded RNA such as that produced by virus replication. An enzyme class is RNase III known as Dicer (which fragments), shown at the top right in blue (PDB file 2ffl ), binds to the dsRNA sequence of cutting the chain small fragments called short interfering RNA (

siRNA), one of which is shown in the upper left (PDB file

2f8s

). The siRNA is about 21 base pairs long, but the two chains are cut in an asymmetrical way: 19 nucleotides are perfectly paired as two nucleotides protruding from each of the two 3 'end. These features readily recognized by the siRNA. It seems that a key role nell'enzima Dicer, is played by special arrangement of four manganese ions, highlighted in magenta in the facility. It is thought that these are just to make the cut in the chain of asymmetric double-stranded RNA, thus creating the projections.

The fragment obtained by the catalyzed by the protein Dicer is associated with an enzyme complex called RISC

(

RNA-interference silencing complex, the RNAi silencing complex ). double-stranded RNA is opened, probably by a helicase, only the antisense RNA strand remains bound to RISC, while the sense strand is degraded. The RISC binds to a complementary sequence of a fragment of mRNA degrading. Why this happens is still under investigation. Probably a

endogenous RNA polymerase somehow manages to feel that a particular messenger RNA is produced in excess through the different reactions we have described to trigger the process of destruction. After all if we think about it is a logic that could also be applied against the virus. In recent years, many industries have arisen that have built kits for RNAi and dsRNA for use in laboratory inactivate genes. In fact, once the known gene sequence of our interest in the double-stranded RNA can be used to produce the siRNA to turn off the gene using RNAi these researchers were able for example to map thousands of genes organism

C .

elegans.

Protein Argonaut siRNA molecules produced by the enzyme Dicer, are also collected by proteins known as the Argonaut and used to destroy any other RNA that are close by. The Argonaut protein, shown here at the bottom (PDB file 1u04) alloy upon himself one of the two chains of siRNA and look for a messenger RNA that is equip with it. If found, it hydrolyzes, that destroys it. In this way, the cell removes all traces of messenger RNA that corresponds to the sequence of the double helix of RNA attached to the top by the enzyme Dicer. Trivia: Argonaut protein was discovered for the first time in a plant mutant that had a spiral shape similar to that of the Nautilus shell, the British call a cephalopod Argonauta. many RNA ...

In the years since the discovery of RNA interference, researchers have found that this process is much more common than expected at the beginning and that small fragments of RNA plays many functional roles. A similar class of molecules called microRNA, is created in the core from the normal RNA of the cell. Even these microRNAs are created by Dicer enzyme and are used to modulate the activity of our normal messenger RNA. Looking for a messenger RNA with a complementary sequence, will bind, and then they stop functioning. MicroRNAs are coupled with complementary sequences of DNA, thus changing the properties of the chromosomes by changing the level of methylation or histone binding.

In the search ...

Scientists have learned to use the technique of RNA interference to destroy specific RNA sequences in animal and plant cells. Exploiting this process, the researchers were able to synthesize artificial interfering RNA sequences which, inserted into the cell, RNA can destroy whatever you want to disable. As mentioned before percmette this technique to study the genes and what may be their function. For example, RNAi is destroyed most of the messenger RNA that produces the gene using RNA interference, which can bind to specific mRNA, thus almost completely stops the production of the protein that is encoded by the gene and observed the consequences. Some researchers are trying to use these small molecules RNA to combat diseases, such as turning off certain genes linked to cancer.

Strategies virus.

viruses, however, have many tricks up their sleeves and rarely left without doing anything when they were attacked. Viruses have developed different strategies to respond to RNA interference. The protein shown here (PDB file

1r9f ) is a protein produced by the suppressor virus tomato bushy rickets.

binds to siRNA and prevents the normal function to destroy the viral messenger RNA. Notice how the protein (in blue) to act as a gauge, overlapping at both ends of the siRNA (orange and red). In this way detects and blocks only small fragments of RNA that have exactly the length of an siRNA.

A look at the structure ...

siRNA molecules produced by the enzyme Dicer are easy to recognize: they all have the same length of 21 base pairs and have an unusual tail of two nucleotides protruding from each end 3 '. The structure shown above in blue (file 1si3 PDB) is the PAZ domain used by many proteins to recognize the two ends of the siRNA. The protein is linked to a short stretch of siRNA represented by small colored balls. Note, in the upper left, as the two bases protruding bind within a small pocket of the protein, while the base terminal of the shorter chain, right, rests just below a ledge of the protein.

Here is a movie of the mechanism of RNA interference directly from the site of still

(

RNA interference mechanism

Sources:

PDB (Protein Data Bank

);

Nature

.