title: Comparative genetics. Systematic discovery of cap-independent translation sequences in human and viral genomes.
abstract: To investigate gene specificity at the level of translation in both the human genome and viruses, we devised a high-throughput bicistronic assay to quantify cap-independent translation. We uncovered thousands of novel cap-independent translation sequences, and we provide insights on the landscape of translational regulation in both humans and viruses. We find extensive translational elements in the 3' untranslated region of human transcripts and the polyprotein region of uncapped RNA viruses. Through the characterization of regulatory elements underlying cap-independent translation activity, we identify potential mechanisms of secondary structure, short sequence motif, and base pairing with the 18S ribosomal RNA (rRNA). Furthermore, we systematically map the 18S rRNA regions for which reverse complementarity enhances translation. Thus, we make available insights into the mechanisms of translational control in humans and viruses.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Weingarten-Gabbay
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Elias-Kirma
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Nir
authors.affiliation: The Delft Bioinformatics Laboratory, Department of Intelligent Systems, Delft University of Technology, Delft, Netherlands. Platform Green Synthetic Biology, Delft, Netherlands. Kluyver Centre for Genomics of Industrial Fermentation, Delft, Netherlands.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Gritsenko
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Stern-Ginossar
authors.affiliation: Department of Computer Science, Technion, Haifa, Israel. Agilent Laboratories, Tel-Aviv, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Adina
authors.initials: A
authors.lastname: Weinberger
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. eran.segal@weizmann.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D020029:Base Pairing; D015967:Gene Expression Regulation, Viral; D015894:Genome, Human / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D000067556:Internal Ribosome Entry Sites / Q000235:genetics; D016296:Mutagenesis; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012315:RNA Caps / Q000235:genetics*; D012328:RNA Viruses / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000067556:Internal Ribosome Entry Sites; D009841:Oligonucleotides; D012315:RNA Caps; D012337:RNA, Ribosomal, 18S