alone or in combination do not serve towards development of a reliable tool for prediction of cellular IRES 14. UTR features such as length, number of upstream AUGs, secondary structure complexity, folding energy etc. However, prediction of cellular IRES remained intractable due to lack of conservation of sequence and/or structure. These tools use structural conservation of IRES, which is observed in a few viral genera and perform prediction using structure comparison approach. In silico tools, such as IRSS and VIPS have been developed for viral IRES secondary structure prediction 12, 13 of which only VIPS is available online. Therefore, attempts have been made to develop algorithms for computational prediction of IRES, which are expected to help experimentalists to narrow down the search space and thereby facilitate discovery of novel IRES. Further, the final outcome from such experimentation, depends on transfection efficiencies, cryptic promoter activity of query sequence(s) and presence of splice sites in them 11. The methods are multifaceted and thus, require skilled personnel. Experimental methods available for detection of IRES presence require multiple cloning, transfection steps and appropriate controls 10. Although, such interventions are yet to be materialized extensively, demonstrating presence of these elements in 5′UTRs, still holds importance. IRES element therefore, has been tested as a potential therapeutic target 9. Similarly, dysfunction of IRES has also been linked to pathophysiological conditions 7, 8. Moreover, IRES mediated initiation has also been reported during vital cellular processes such as mitotic cycle and apoptosis 5, 6. Therefore, IRES plays an important role in viral replication and development of integrated stress response. However, some viral and a subset of cellular transcripts encoding stress responsive and regulatory proteins, are translated through IRES mediated internal initiation mechanism. During viral infections and cytoplasmic stresses, global cellular translation is inhibited through a variety of mechanisms 1. Presence of IRES was first experimentally demonstrated in viruses of Picornaviridae family 3, 4. An element present in 5′UTR of these messages, called IRES, is known to facilitate such internal initiation 2. Alternatively, for some transcripts, translation can initiate internally in a cap-independent manner. The ribosomal subunit then scans the mRNA until it reaches start codon 1. Then, the cap binding complex composed of eIF4A, eIF4E and eIF4G recruits the pre-initiation complex to the cap structure (m 7G). Met-tRNA i together forms the 43S pre-initiation complex.For such initiation, the 40S ribosomal subunit along with eukaryotic initiation factors (eIFs) namely eIF1, eIF1A, eIF3, eIF5 and the ternary complex comprising eIF2 Translation initiation in eukaryotes occurs principally in a 5′cap-dependent manner. The IRESPred server is freely available at. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. Experimental demonstration of IRES in UTR remains a challenging task. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5′ untranslated regions (UTRs). However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. Cellular mRNAs are predominantly translated in a cap-dependent manner.
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