Research Article

Systematic discovery of cap-independent translation sequences in human and viral genomes

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Science  15 Jan 2016:
Vol. 351, Issue 6270, aad4939
DOI: 10.1126/science.aad4939

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  • RE: Internal initiation of translation writ large
    • Stephen D, Baird, Manager HTS Lab, Children's Hospital of Eastern Ontario Research Institute
    • Other Contributors:
      • Martin Holcik, Scientist, Children's Hospital of Eastern Ontario Research Institute
      • Zachary King, Physician

    In the article “Systematic discovery of cap-independent translation sequences in human and viral genomes” (15 January 2016 )(1) Weingarten-Gabby et al. surveyed a large number of mRNA-derived 210 bp segments for their ability to internally initiate translation. Our own search for IRESes with a secondary structure similar to that of a known IRES from XIAP mRNA identified two new IRESes but, surprisingly, with little notable structure similarity (2). Was that serendipity? We therefore wondered how prevalent IRESes are within the human transcriptome, and asked how many IRESes are there if we test 10 random UTRs. We selected 10 random 5'-UTRs from the UTRdb (3) using a perl script with a randomization function and tested their ability to initiate internal initiation using a previously characterized beta-gal/CAT bicistronic reporter system (4). We identified one UTR from ZNF584 that showed bona fide IRES activity (without any cryptic promoter or splicing activity) but missed two IRESes discovered by the systematic survey (TEX2 and ZNF146). This is because the UTRs were improperly annotated at the time of our cloning; theoretically we had 3 genes out of 10 with IRES elements, or 30% of transcriptome, which is a bit higher than the 10% reported by the survey. While Weingarten-Gabby et al.'s test of small segments may have missed large structural IRESes like HCV, their discovery of so many IRES elements shows the IRES mechanism as a common feature, and that it frequently...

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    Competing Interests: None declared.