Alternative Mechanisms to Initiate Translation in Eukaryotic mRNAs

Abstract

<jats:p>The composition of the cellular proteome is under the control of multiple processes, one of the most important being translation initiation. The majority of eukaryotic cellular mRNAs initiates translation by the cap-dependent or scanning mode of translation initiation, a mechanism that depends on the recognition of the m<jats:sup>7</jats:sup>G(5<jats:sup>′</jats:sup>)ppp(5<jats:sup>′</jats:sup>)N, known as the cap. However, mRNAs encoding proteins required for cell survival under stress bypass conditions inhibitory to cap-dependent translation; these mRNAs often harbor internal ribosome entry site (IRES) elements in their 5<jats:sup>′</jats:sup>UTRs that mediate internal initiation of translation. This mechanism is also exploited by mRNAs expressed from the genome of viruses infecting eukaryotic cells. In this paper we discuss recent advances in understanding alternative ways to initiate translation across eukaryotic organisms.</jats:p>

Picornavirus IRES elements: RNA structure and host protein interactions

“…Subsequent studies demonstrated that IRES elements drive internal initiation of translation in the RNA of all members of the Picornaviridae family (Bakhshesh et al, 2008;Borman and Jackson, 1992;Brown et al, 1991;Hinton and Crabb, 2001;Hinton et al, 2000;Kaku et al, 2002;Kuhn et al, 1990;Nateri et al, 2000;Sweeney et al, 2012;Willcocks et al, 2011;Yu et al, 2011b). The genome of other RNA viruses also contains IRES elements, as illustrated by hepacivirus, pestivirus, dicistrovirus, retrovirus Tsukiyama-Kohara et al, 1992;Vallejos et al, 2010;Wilson et al, 2000), as well as some RNA viruses infecting plants and protozoa (reviewed in Martinez-Salas et al, 2012). Although the presence of an IRES element is a common feature of all picornavirus RNAs, some differences affecting the organization of the 5 UTR, described below, are specific of each genus.…”

Position of the kissing-loop interaction associated with PTE-type 3′CITEs can affect enhancement of cap-independent translation

“…Many animal RNA viruses conduct cap-independent translation by attracting ribosomes to extensive, highly structured cis-acting RNA elements known as internal ribosome entry sites (IRES). Viral IRES are located near , or span the initiation codon and recruit required initiation factors or ribosomal subunits directly (Hertz and Thompson, 2011; Martinez-Salas et al, 2012). Plant viruses can also contain 5’ IRES, which for Tobacco etch potyvirus recruits eIF4G within the eIF4F complex as well as the 40S ribosomal subunit for initiation of polyprotein translation (Basso et al, 1994; Gallie, 2001).…”

Using RNA inverse folding to identify IRES-like structural subdomains

“…Although most cellular mRNAs initiate translation by a cap-dependent mechanism, alternative mechanisms are operative when cap-dependent translation is compromised, including IRES-dependent translation initiation. 3,4,28 Most known IRES elements are located in the 5′ UTR of mRNAs upstream of the initiator codon, but some exceptions exist. [29][30][31][32] Furthermore, although cellular IRES elements described so far lack conserved structural features, 3,4 RNA structure plays a fundamental role in viral IRES-dependent translation initiation.…”