IRES elements were first discovered in the mRNAs of the virus family Picornaviridae, which have a long highly structured 5'UTR that lacks a methylated cap structure at the 5' end. In contrast to the scanning model, IRES can form specific secondary and tertiary structures and interact directly with the translational machinery beyond the AUG start codon. This is termed as the cardinal rule or the first AUG rule. For most eukaryotic mRNAs, the first AUG encountered by the translation initiation complex acts as the initiation codon. The translational scanning machine, comprising the 40S ribosomal subunit and a cap-binding initiation factor complex (eIF4F, composed of eIF4E, eIF4G, and eIF4A), recognizes and binds to the 5' end methylated cap structure of mRNA and scans linearly downstream until it reaches an AUG codon embedded in an optimum context for the initiation of protein translation initiation. Initiation of protein translation in eukaryotes is governed by a cap- and 5' end-dependent mechanism, the scanning model, or can be mediated by a cap- and 5' end-independent manner through an RNA element termed as "internal ribosomal entry site" (IRES). This new search approach for IRES elements will provide a useful research tool on IRES related studies. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. IRSS is freely available at this website. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method and the RNA Align program, used to compare predicted structures. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. Most existing RNA structure prediction programs are unable to deal with IRES elements. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells.
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