Ires sequences12/7/2023 ![]() For instance, an IRES can be a short 9 nt-long sequence ( 6) and can also be a large highly structured 600 nt-long sequence ( 7, 8). The mechanism of internal entry of ribosomes is not fully elucidated because IRES sequences are very diverse. More importantly, evidence that internal entry of ribosomes is controlled during the cell cycle or apoptosis demonstrates the importance of this new mechanism of translation initiation and suggests that internal entry of ribosomes could be a key player of cellular proliferation and/or differentiation ( 4, 5). The important feature is that cellular IRESes are found in crucial messenger RNAs encoding key regulatory proteins (transcription factors, growth factors and kinases). There is also a continuously growing list of IRES-containing cellular mRNAs. Indeed, IRESes not only exist in picornaviruses but are also present in flaviviruses, plant viruses, retroviruses and even DNA viruses. However, the process of internal entry of ribosomes appears to be far more extended than previously described. While the role of the 5′ cap structure and the 3′ poly(A) tail in translation initiation were directly envisaged to be of general importance, the role of an Internal Ribosome Entry Sites (IRES) sequence was initially thought to be restricted to the picornavirus group. These three features can act either together or independently, depending on the mRNA or the cell status, to recruit the small subunit of the ribosome. The first step in eukaryotic translation initiation, which consists in the recruitment of the 40S small ribosomal subunit to the eukaryotic messenger RNA (mRNA), requires several features of RNA polymerase II-transcribed mRNAs: (i) the 7methyl guanosine capped structure at the 5′ end, (ii) the poly(A) tail at the 3′ end and (iii) the internal ribosome entry site located upstream of the translation initiation codon ( 1– 3). Several subsets of data are classified according to the viral taxon (for viral IRESes), to the gene product function (for cellular IRESes), to the possible cellular regulation or to the trans-acting factor that mediates IRES function. The IRES database is a comprehensive Sequences are presented in FASTA form and hotlinked to NCBI GenBank files. Novel IRES sequences continue to be added to public databases every year and the list of unknown IRESes is certainly still very large. These sequences are very diverse and are present in a growing list of mRNAs. All rights reserved.Internal Ribosome Entry Sites (IRES) are cis-acting RNA sequences able to mediate internal entry of the 40S ribosomal subunit on some eukaryotic and viral messenger RNAs upstream of a translation initiation codon. Host factors IRES elements RNA structure RNA–protein interactions Translation control Untranslated regions.Ĭopyright © 2015 Elsevier B.V. This review is focused to describe recent advances on the studies of RNA structure and RNA-protein interactions modulating picornavirus IRES activity. However, given their large diversity and complexity, the mechanistic basis of its mode of action is not yet fully understood. Picornavirus IRES are amongst the most potent elements described so far. Many of these factors suffer important modifications during infection including cleavage by picornavirus proteases, changes in the phosphorylation level and/or redistribution of the protein from the nuclear to the cytoplasm compartment. These elements are cis-acting RNA sequences that adopt diverse three-dimensional structures and recruit the translation machinery using a 5' end-independent mechanism assisted by a subset of translation initiation factors and various RNA binding proteins termed IRES transacting factors (ITAFs). Internal ribosome entry site (IRES) elements were discovered in picornaviruses. ![]()
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