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

Identifying the IRESs of humans and viruses Most proteins result from the translation of 5′ capped RNA transcripts. In viruses and a subset of human genes, RNA transcripts with internal ribosome entry sites (IRESs) are uncapped. Weingarten-Gabbay et al. systematically surveyed the presence of IRESs in human protein-coding transcripts, as well those of viruses (see the Perspective by Gebauer and Hentze). Large-scale mutagenesis profiling identified two classes of IRESs: those having a functional element localized to one small region of the IRES and those with important elements distributed across the entire region. An unbiased screen across human genes suggests that IRESs are more frequent than previously supposed in 3′ untranslated regions. Science , this issue p. 10.1126/science.aad4939 ; see also p. 228