RNA regulons in Hox 5' UTRs confer ribosome specificity to gene regulation

Nature. 2015 Jan 1;517(7532):33-8. doi: 10.1038/nature14010. Epub 2014 Nov 19.


Emerging evidence suggests that the ribosome has a regulatory function in directing how the genome is translated in time and space. However, how this regulation is encoded in the messenger RNA sequence remains largely unknown. Here we uncover unique RNA regulons embedded in homeobox (Hox) 5' untranslated regions (UTRs) that confer ribosome-mediated control of gene expression. These structured RNA elements, resembling viral internal ribosome entry sites (IRESs), are found in subsets of Hox mRNAs. They facilitate ribosome recruitment and require the ribosomal protein RPL38 for their activity. Despite numerous layers of Hox gene regulation, these IRES elements are essential for converting Hox transcripts into proteins to pattern the mammalian body plan. This specialized mode of IRES-dependent translation is enabled by an additional regulatory element that we term the translation inhibitory element (TIE), which blocks cap-dependent translation of transcripts. Together, these data uncover a new paradigm for ribosome-mediated control of gene expression and organismal development.

Publication types

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

MeSH terms

  • 5' Untranslated Regions / genetics*
  • Animals
  • Bone and Bones / embryology
  • Bone and Bones / metabolism
  • Cell Line
  • Conserved Sequence
  • Evolution, Molecular
  • Gene Expression Regulation / genetics*
  • Genes, Homeobox / genetics*
  • Mice
  • Molecular Sequence Data
  • Protein Biosynthesis / genetics
  • RNA Caps / metabolism
  • Regulatory Sequences, Ribonucleic Acid / genetics*
  • Ribosomal Proteins / metabolism
  • Ribosomes / chemistry
  • Ribosomes / metabolism*
  • Substrate Specificity
  • Zebrafish / genetics


  • 5' Untranslated Regions
  • RNA Caps
  • RPL38 protein, mouse
  • Regulatory Sequences, Ribonucleic Acid
  • Ribosomal Proteins

Associated data

  • GENBANK/KM596709