A search for structurally similar cellular internal ribosome entry sites.
Internal ribosome entry sites (IRES) allow ribosomes to be recruited to mRNA in a cap-independent manner. Some viruses that impair cap-dependent translation initiation utilize IRES to ensure that the viral RNA will efficiently compete for the translation machinery. IRES are also employed for the translation of a subset of cellular messages during conditions that inhibit cap-dependent translation initiation. IRES from viruses like Hepatitis C and Classical Swine Fever virus share a similar structure/function without sharing primary sequence similarity. Of the cellular IRES structures derived so far, none were shown to share an overall structural similarity. Therefore, we undertook a genome-wide search of human 5'UTRs (untranslated regions) with an empirically derived structure of the IRES from the key inhibitor of apoptosis, X-linked inhibitor of apoptosis protein (XIAP), to identify novel IRES that share structure/function similarity. Three of the top matches identified by this search that exhibit IRES activity are the 5'UTRs of Aquaporin 4, ELG1 and NF-kappaB repressing factor (NRF). The structures of AQP4 and ELG1 IRES have limited similarity to the XIAP IRES; however, they share trans-acting factors that bind the XIAP IRES. We therefore propose that cellular IRES are not defined by overall structure, as viral IRES, but are instead dependent upon short motifs and trans-acting factors for their function.
Baird
Stephen D
SD
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada.
Lewis
Stephen M
SM
Turcotte
Marcel
M
Holcik
Martin
M
D020121:5' Untranslated Regions / Q000737:chemistry* / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics
D020121:5' Untranslated Regions; D051401:Aquaporin 4; D004268:DNA-Binding Proteins; C111027:NKRF protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein