Structural Biochemistry/Nucleic Acid/RNA/RNA-Dependent RNA Polymerase

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RNA-dependent RNA polymerase is an enzyme, which catalyzes the replication of RNA from an RNA template. Usually, the typical RNA polymerase is well known that are catalyzes the transcription of mature RNA from a DNA template.

Virus[edit]

The most famous RdRP in a virus is the polio virus 3Dpol. The virus is made up of RNA which enters the cell through receptor-mediated endocytosis. The RNA is able to act as a template for complementary RNA synthesis. The complementary strand of the RNA is able to act as a template, in order to produce new viral genomes which are packaged and prepare to lyse from the cell transfer to other cells for more infection. This method of replication there is no DNA; therefore the replication is rapidly.However, the downside is that there is no 'back-up' DNA copy.

There is several eukaryotes that have RdRPs, and the RdRPs are involved in RNA interference; these amplify microRNAs and small temporal RNAs. Also, they produce double-stranded RNA from using the small interfering RNAs as primers. The RdRPs are used in the defense mechanisms, but it can be usurped by RNA viruses for their benefit.

Polio Virus[edit]

The first interaction for the polio virus is with a host cell; it consists two materials: binding to a specific cell surface protein, and the poliovirus receptor (PVR). The PVR, is a cell surface sialylated glycoprotein, and is a member of the immunoglobulin superfamily (is a loop in the stucture of the protein that is a Ig domain). Therefore, PVR has three Ig loops that are on the outside of the cell. The loops begins with the most farthest of the cell surface. In loop 1, the polio virus binds to it receptor, which the receptor molecule binds on the virus particle.

The poliovirus genome is made of positive sense single stranded RNA that encodes a polyprotein of aa's in the range of 2100-2400. Both ends of the genome are modified; in the 5' end is modify by a covalently attached basic protein VPg which consist of 23 aa's, and the 3' end by polyadenylation. In a series of cleavages, viral proteases cleave themselves out and break down the polyprotein into 10 separate gene products involved in replication and packaging.

The viral proteases 2A cleaves the p220 subunit of the cap binding complex; therefore, they make host cell from the mRNA unrecognizable to ribosomes. The 2A protease abrogates most of the host cell's own protein synthesis. Viral mRNA depends on a 5' UTR that contains an internal ribosome entry site; serves as a ribosome docking site to the subunits of ribosomes.

File:RDR Polio.jpg
The Structure of RDR in Polio

Replication occurs entirely in the cytoplasm. In addition, they serve as a template for protein synthesis, the positive sense strand genome is utilized as a template for the synthesis negative sense strands. On the other hand, the host cells has a lack of necessities to replicate RNA. Poliovirus uses a viral RNA-dependent RNA polymerase to produce RNA molecules of the opposite polarity. Viral protein VPg covalently attached to uridine, which serves as the primer. The first round of replication produces a single antisense molecule. The antisense template is used to produce copies of the original genome, which they are packaged into viral capsids before it gets release.

The virus has been translated to its own RNA, so it produce the necessary proteins, and the virus genome is replicated. However, the virus needs to package the newly synthesized RNA molecules inside capsids, and must need the RNA packaged in order the virus is completed. The capsid proteins self-assemble into an immature capsid that has a structure of which proteins were needed, but the final form of the virus is not finished to cleaved. The mature poliovirus capsid has icosahedral symmetry, and have 60 copies of viral capsid proteins that are VP1, VP2, VP3, and VP4. The viral RNA enters the incomplete capsid and is secured inside when the viral proteases make the final cleavages. Once the genomes have been packaged into mature virions, the virus particles await the cell's lysis in order to be released. As many as 100,000 virions can be released from a single infected cell.

There is a conformational changes in the capsid, because there was a binding in the virus with the receptor. VP4, an internal capsid protein detaches from the capsid. The capsid swells and the poliovirus genome is susceptible to degradation. When VP1 is released, the genome is released onto the cytoplasm of the cell. The viral entry strategy is very inefficient; only 1% of the viruses initiate an infection.

External[edit]

http://www.brown.edu/Courses/Bio_160/Projects2000/Polio/PoliovirusLifeCycle.htm