Protein translation of most eukaryotic mRNA

Messenger RNA

Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

s requires association of Met-tRNA, several eukaryotic initiation factors, and GTP

Guanosine triphosphate

Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

 with the 40S ribosomal subunit. The ribosome can only bind the capped mRNA after binding to the initiator tRNA. Translation of hepatitis C virus

Hepatitis C virus

Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...

 (HCV) mRNA is initiated by a different mechanism from the usual 5' cap-binding model. This alternate mechanism relies on the direct binding of the 40S ribosomal subunit by the internal ribosome entry site

Internal ribosome entry site

An internal ribosome entry site, abbreviated IRES, is a nucleotide sequence that allows for translation initiation in the middle of a messenger RNA sequence as part of the greater process of protein synthesis...

 (IRES) in the 5' UTR of HCV RNA. HCV IRES adopts a complex structure, and may differ significantly from IRES elements

Picornavirus internal ribosome entry site (IRES)

This family represents the Picornavirus internal ribosome entry site . IRES elements allow cap and end-independent translation of mRNA in the host cell. It has been found that La autoantigen is required for Coxsackievirus B3 IRES-mediated translation, and it has been suggested that La may be...

 identified in picornavirus

Picornavirus

A picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped, positive-stranded RNA viruses with an icosahedral capsid. The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase...

es. A small number of eukaryotic mRNA have been shown to be translated by internal ribosome entry.

IRES structure

Nucleotides 1-40 of the HCV mRNA are thought not to contribute to translation, and are rather required for genomic

Genome

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 replication. The remainder of the HCV 5'-UTR consists of three domains, namely domains II-IV (domain I is located on the 5'-end of the mRNA).

Mechanism of action

HCV IRES binds independently two components of eukaryotic translation initiation machinery, protein eIF3 and 40S

40S

40S is the small subunit of eukaryotic ribosomes.It interacts with the internal ribosome entry site of the hepatitis C virus.The following is a list of proteins contained in the 40S ribosome:...

 small ribosome subunit. Moreover, it binds 40S in such a manner that AUG initiator codon is positioned in ribosomal P-site, thus no ribosomal scanning is required. Consequently scanning factors eIF1 and eIF1A are dispensable for the HCV translation. And so are factors generally required for mRNA binding and unwinding of 5'-UTR, eIF4A

Eif4a

The eukaryotic initiation factor-4A family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits...

, eIF4B

EIF4B

Eukaryotic translation initiation factor 4B is a protein that in humans is encoded by the EIF4B gene.-External links:* from Nature Reviews Microbiology. A good image and overview of the function of initiation factors-Further reading:...

 and eIF4F.
Initiator tRNA is brought then either by eIF2

EIF2

Eukaryotic Initiation Factor 2 is a eukaryotic initiation factor. It is required in the initiation of translation. In this fundamental process of life, the ribosome builds proteins according to the information encoded on the mRNA. eIF2 mediates the binding of tRNAmet to the ribosome in a...

 or, in stress conditions when eIF2 is inactivated, by eIF5B

EIF5B

Eukaryotic translation initiation factor 5B is a protein that in humans is encoded by the EIF5B gene.-Further reading:...

, homologoue of prokaryotic IF2 protein.