Internal ribosome entry site
As an IRES (internal ribosomal entry site, Eng. Internal ribosomal entry site ) is in cell biology refers to a specific folding (secondary structure) of the messenger RNA that mediates the binding of mRNA to the ribosome without further so-called initiation factors. Thus, the synthesis of proteins, the so-called translation start immediately by the center of a mRNA. IRES have been described in some genes of eukaryotes and their viruses.
Properties
Usually carry a cellular mRNAs specifically tailed nucleotide at its 5 'end, the so-called 5' cap structure to, together with other cellular factors to mediate the binding of the eukaryotic ribosome and initiate protein synthesis. Some cellular mRNAs in eukaryotes (eg for the oncogene c -Myc, ornithine decarboxylase, the fibroblast growth factor 2 or the Endothelial Growth Factor ) are excluded from this complex control system can be made using an IRES directly to the 40S subunit the ribosomes bind the protein and initiate protein synthesis.
Some IRES also be placed in the context of diseases, the loss of function of an IRES element to the mRNA of the connexin 32 gene seems to be a main cause of the Charcot-Marie -Tooth disease.
The mechanisms of viral IRES are more extensive than the characterized eukaryotic. The IRES of hepatitis C virus binds directly to the P site of the 40S ribosomal subunit therefore need this IRES no eukaryotic initiation factors such as eIF1, 1A, 4A, 4B and 4E. The picornavirus IRES binds to the 40S over eIF4 subunit. Many viral and eukaryotic IRES require other cellular proteins, which are referred to as IRES -trans -acting factors ( ITAFs ).
Viral IRES
Some RNA viruses also possess an IRES to start the production of viral proteins independently of cellular factors. This applies, for example, hepatitis C virus and the picornaviruses (e.g. poliovirus ). While poliovirus IRES structure was also first detected, since it is completely blocked in the cell culture, the synthesis of cellular proteins in favor of viral products. This is accomplished by cleavage of initiation factor eIF4G by viral enzymes, which only mRNAs with IRES, ie mainly the viral RNA can be transcribed into protein. A variant of the IRES occurs in Dicistroviridae.
Types
Applications
IRES elements are also used in the course of a vector designs, for example, the co-expression of a reporter gene to monitor the transfection or transduction. In this case, the gene to be cloned is set usually before the IRES ( 5 ' direction), the reporter gene behind. Expression of the reporter gene is the synthesis of mRNA in full length.
History
The IRES was first described in 1988 in the RNA genome of poliovirus and encephalomyocarditis virus in the laboratories of Nahum Sonenberg and Eckard Wimmer. The process of internal translation initiation site was designated as internal initiation of translation.