Correlation Engine 2.0
Clear Search sequence regions


  • eIF1 (2)
  • eIF5 (2)
  • elements (1)
  • factors (1)
  • genes (6)
  • homeobox (7)
  • homeostasis (1)
  • inhibit (1)
  • mice (1)
  • nucleotides (1)
  • open (4)
  • paralogs (1)
  • protein biosynthesis (1)
  • puromycin (1)
  • ribosome (2)
  • rna (5)
  • start codon (4)
  • subunit protein (1)
  • Sizes of these terms reflect their relevance to your search.

    Translation start site selection in eukaryotes is influenced by context nucleotides flanking the AUG codon and by levels of the eukaryotic translation initiation factors eIF1 and eIF5. In a search of mammalian genes, we identified five homeobox (Hox) gene paralogs initiated by AUG codons in conserved suboptimal context as well as 13 Hox genes that contain evolutionarily conserved upstream open reading frames (uORFs) that initiate at AUG codons in poor sequence context. An analysis of published cap analysis of gene expression sequencing (CAGE-seq) data and generated CAGE-seq data for messenger RNAs (mRNAs) from mouse somites revealed that the 5' leaders of Hox mRNAs of interest contain conserved uORFs, are generally much shorter than reported, and lack previously proposed internal ribosome entry site elements. We show that the conserved uORFs inhibit Hox reporter expression and that altering the stringency of start codon selection by overexpressing eIF1 or eIF5 modulates the expression of Hox reporters. We also show that modifying ribosome homeostasis by depleting a large ribosomal subunit protein or treating cells with sublethal concentrations of puromycin leads to lower stringency of start codon selection. Thus, altering global translation can confer gene-specific effects through altered start codon selection stringency. Copyright © 2022 the Author(s). Published by PNAS.

    Citation

    Ivaylo P Ivanov, James A Saba, Chen-Ming Fan, Ji Wang, Andrew E Firth, Chune Cao, Rachel Green, Thomas E Dever. Evolutionarily conserved inhibitory uORFs sensitize Hox mRNA translation to start codon selection stringency. Proceedings of the National Academy of Sciences of the United States of America. 2022 Mar 01;119(9)

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 35217614

    View Full Text