Internal ribosome entry site

An internal ribosome entry site, abbreviated IRES, is a RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at the 5' end of mRNA molecules, since 5' cap recognition is required for the assembly of the initiation complex. The location for IRES elements is often in the 5'UTR, but can also occur elsewhere in mRNAs.

IRES sequences were first discovered in 1988 in the poliovirus (PV) and encephalomyocarditis virus (EMCV) RNA genomes in the labs of Nahum Sonenberg and Eckard Wimmer, respectively. They are described as distinct regions of RNA molecules that are able to recruit the eukaryotic ribosome to the mRNA. This process is also known as cap-independent translation. It has been shown that IRES elements have a distinct secondary or even tertiary structure, but similar structural features at the levels of either primary or secondary structure that are common to all IRES segments have not been reported to date.

In recent years it has become common for molecular biologists to insert IRES sequences into their vectors to allow for expression of two genes from a single vector—for example, a transgene and a fluorescent reporter molecule. The first gene is initiated at the normal 5' cap, and the second at the IRES.

IRESs are commonly located in the 5'UTR of RNA viruses and allow translation of the RNAs in a cap-independent manner. However, mRNAs of viruses from Dicistroviridae family possess two open reading frames (ORFs), and translation of each is directed by two distinct IRESs. It has also been suggested that some mammalian cellular mRNAs also have IRESs. These cellular IRES elements are thought to be located in eukaryotic mRNAs encoding genes involved in stress , and other processes critical to survival. As of September 2009, there are 60 animal and 8 plant viruses reported to contain IRES elements and 115 mRNA sequences containing them as well.

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