Internal ribosome entry site

An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis.

IRES sequences were first discovered in 1988 in the poliovirus (PV) and encephalomyocarditis virus (EMCV) RNA genomes in the laboratories of Nahum Sonenberg[1] and Eckard Wimmer,[2] respectively.

Use of IRES sequences in molecular biology soon became common as a tool for expressing multiple genes from a single transcriptional unit in a genetic vector.

The mRNA of viruses of the Dicistroviridae family possess two open reading frames (ORFs), and translation of each is directed by a distinct IRES.

Interaction between these two eukaryotic initiation factors (eIFs) of the eIF4F complex is necessary for 40S ribosomal subunit recruitment to the 5' end of mRNAs, which is further thought to occur with mRNA 5'cap to 3' poly(A) tail loop formation.

[10] A promoter or splice acceptor within a test sequence can result in the production of monocistronic mRNA from which the downstream cistron is translated by conventional cap-dependent, rather than IRES-mediated, initiation.

A later study that documented a variety of unexpected aberrant mRNA species arising from reporter plasmids revealed that splice acceptor sites can mimic both IRES and promoter elements in tests employing such plasmids, further highlighting the need for caution in the interpretation of reporter assay results in the absence of careful RNA analysis.

[11] IRES sequences are often used in molecular biology to co-express multiple genes under the control of the same promoter, thereby mimicking a polycistronic mRNA.

Within the past decades, IRES sequences have been used to develop hundreds of genetically modified rodent animal models.