Abstract
It is now known that cap-independent translation initiation facilitated by internal ribosome entry sites (IRESs) is vital in selective cellular protein synthesis under stress and different physiological conditions. However, three problems make it hard to understand transcriptome-wide cellular IRES-mediated translation initiation mechanisms: (i) complex interplay between IRESs and other translation initiation–related information, (ii) reliability issue of in silico cellular IRES investigation and (iii) labor-intensive in vivo IRES identification. In this research, we constructed the Human IRES Atlas database for a comprehensive understanding of cellular IRESs in humans. First, currently available and suitable IRES prediction tools (IRESfinder, PatSearch and IRESpy) were used to obtain transcriptome-wide human IRESs. Then, we collected eight genres of translation initiation–related features to help study the potential molecular mechanisms of each of the putative IRESs. Three functional tests (conservation, structural RNA–protein scores and conditional translation efficiency) were devised to evaluate the functionality of the identified putative IRESs. Moreover, an easy-to-use interface and an IRES–translation initiation interaction map for each gene transcript were implemented to help understand the interactions between IRESs and translation initiation–related features. Researchers can easily search/browse an IRES of interest using the web interface and deduce testable mechanism hypotheses of human IRES-driven translation initiation based on the integrated results. In summary, Human IRES Atlas integrates putative IRES elements and translation initiation–related experiments for better usage of these data and deduction of mechanism hypotheses. Database URL: http://cobishss0.im.nuk.edu.tw/Human_IRES_Atlas/
Highlights
Cells in proliferation adapt their metabolism to environmental stimuli through the regulation of protein synthesis, and translational regulation can provide instant protein level adjustment for handling sudden environmental changes and stress responses [1]
Cellular internal ribosome entry sites (IRESs) elements are known to be closely related to selective cellular protein synthesis under stress and physiopathological conditions [7] and can have profound effects on human tumor cells [8]
A novel database called Human IRES Atlas was constructed to deposit the systematic in silico identified IRESs from the human transcriptome
Summary
Cells in proliferation adapt their metabolism to environmental stimuli through the regulation of protein synthesis, and translational regulation can provide instant protein level adjustment for handling sudden environmental changes and stress responses [1]. Available and suitable IRES prediction tools were used to identify the putative IRES elements in the human transcriptome To evaluate their potential as functional IRESs, three functionality tests were conducted for each of the putative cellular IRES elements: sequence conservation (among different mammalian species), structural RPI scores and conditional translation efficiency (Figure 1b). The following contents were collected and integrated in this repository: translation initiation site (TIS) probing experiments, uORF sequences, sequence conservation scores (among mammalian species), ribosome profiling data, structure information of the IRES elements, experimentally identified ITAF target sequences, IRES activity bicistronic measurements and literature-curated IRES verification experiment evidence. Based on the understanding of cellular IRES elements, three functionality tests are performed with the collected data in this database: conservation, structural RPI scores and conditional translation efficiency between stressed and normal states. IRES data and the related datasets were deposited through MySQL
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