IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES)

Pandurang Kolekar,Abhijeet Pataskar,Urmila Kulkarni-Kale,Jayanta Pal,Abhijeet Kulkarni

doi:10.1038/srep27436

Pandurang Kolekar, Abhijeet Pataskar + Show 3 more

Open Access

https://doi.org/10.1038/srep27436

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Journal: Scientific Reports	Publication Date: Jun 6, 2016
Citations: 49	License type: CC BY 4.0

Affiliation: Savitribai Phule Pune University

Abstract

Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5′ untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). 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). 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. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/.

Highlights

Presence of Internal ribosome entry sites (IRES) was first experimentally demonstrated in viruses of Picornaviridae family[3,4]
The state-of-the-art understanding of IRES and widely accepted theories specify that i) housekeeping gene messages, principally follow the cap dependent initiation pathway[15] whereas, internal initiation process is confined to some viral, and cellular transcripts which encode regulatory and stress responsive proteins and ii) IRES element present in untranslated regions (UTRs) of these transcripts contests cap-dependent initiation for components of translation machinery including ribosomes[2]
These studies are restricted to viral IRES (HCV and Cricket Paralysis virus (CrPV)) and direct interactions between 40S ribosomal subunit proteins and cellular IRES elements have not yet been demonstrated experimentally

Summary

Introduction

Presence of IRES was first experimentally demonstrated in viruses of Picornaviridae family[3,4]. Some viral and a subset of cellular transcripts encoding stress responsive and regulatory proteins, are translated through IRES mediated internal initiation mechanism. In the present study, an attempt has been made to utilize the interaction probabilities of 27 different small-subunit ribosomal proteins (SSRPs) with 5′UTR sequences by determining if these features possess information content to classify UTRs as IRES positive (IP) or negative (IN). In addition to these 27 features, we used 8 general features of UTR to complement the classification. The comparison of IRESPred with VIPS, the only available server for prediction of viral IRES is presented

Methods

Results

Conclusion