PUBLICATION

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

Authors
Xue, S., Tian, S., Fujii, K., Kladwang, W., Das, R., Barna, M.
ID
ZDB-PUB-150127-16
Date
2015
Source
Nature   517: 33-8 (Journal)
Registered Authors
Keywords
none
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
PubMed
25409156 Full text @ Nature
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping