A bioinformatical approach to the analysis of viral and cellular internal ribosome entry sites

Martin Mokrejš1,*, Václav Vopálenský1, Tomáš Mašek1 and Martin Pospíšek1,*
1Department of Genetics and Microbiology, Charles University, Faculty of Science, Viničná 5, 128 43 Prague, Czech Republic

The internal ribosome entry site (IRES) is a part of the mRNA sequence which is able to attract the eukaryotic ribosomal initiation complex and to directly promote the initiation of protein synthesis independently of the presence of 5'-terminal 7mG cap. RNA structures bearing the IRES activity were first discovered in certain eukaryotic viruses where they very often play a pivotal role in viral strategies, allowing the viral invader to overcome the overall decrease of the host protein synthesis caused either by viral proteins or by the cellular antiviral defense system. Although the IRES segments and thus the cap-independent translation initiation were first described in viruses, extensive evidence has appeared in the past few years that a similar principle of the translation initiation is utilized also by some cellular mRNAs. Demonstration of IRES activity of a particular RNA region is not a simple task. A proper design of the experiment and a careful selection of the controls - excluding artificial signals generated by leaky scanning, ribosome hopping and undesirable cryptic transcription, splicing or physical breakage at the hot-spots - are very important. A number of false positives described in the literature as well as difficulties in designing appropriate controls have become the major stimuli for creating IRESite - the publicly available manually annotated database of experimentally verified IRES structures. This chapter presents the current status of the IRESite database (http://www.iresite.org), the complete list of known viral and cellular IRESs as well as novel results obtained from the comparative analyses of IRES segments accumulated to date. The article also presents a brief description and comparison of other available databases containing IRES and 5' untranslated region (5'-UTR) related information.

*Corresponding authors: M. Mokrejš <mmokrejs --at-- iresite.org>, M. Pospíšek <martin --at-- natur.cuni.cz>

Full citation
Mokrejs M., Vopalensky V., Masek T., Pospisek M. (2007) Title: A Bioinformatical Approach to the Analysis of Viral and Cellular Internal Ribosome Entry Sites. In: Columbus F editors. New Messenger RNA Research Communications. Hauppauge, NY: Nova Science Publishers; pp. 133-166.