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

Science. 2016 Jan 15;351(6270):aad4939. doi: 10.1126/science.aad4939. Epub 2016 Jan 14.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 5' Untranslated Regions / genetics
  • Base Pairing
  • Gene Expression Regulation, Viral
  • Genome, Human / genetics*
  • Genome, Viral / genetics*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Internal Ribosome Entry Sites / genetics
  • Mutagenesis
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • Protein Biosynthesis / genetics*
  • RNA Caps / genetics*
  • RNA Viruses / genetics
  • RNA, Ribosomal, 18S / genetics
  • RNA, Ribosomal, 18S / metabolism
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, RNA / methods

Substances

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Internal Ribosome Entry Sites
  • Oligonucleotides
  • RNA Caps
  • RNA, Ribosomal, 18S

Associated data

  • GEO/GSE74277