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| Status |
Public on Feb 21, 2022 |
| Title |
Evolutionarily Conserved Inhibitory uORFs Sensitize Hox mRNA Translation to Start Codon Selection Stringency |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
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 human genes, we identified 5 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. We analyzed published CAGE-seq data and generated CAGE-seq data from mRNAs from mouse somites. These data demonstrate that the 5’ leaders of Hox mRNAs of interest contain conserved uORFs, are much shorter than reported, and lack previously proposed IRES 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.
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| Overall design |
nAnT-iCAGE sequencing data from somite/neural tubes isolated from three E11.5 C56BL/6J mouse embryos
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| Contributor(s) |
Ivanov IP, Saba JA, Fan C, Firth AE, Cao C, Green R, Dever TE |
| Citation(s) |
35217614 |
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| Submission date |
Sep 21, 2021 |
| Last update date |
Mar 09, 2022 |
| Contact name |
James Saba |
| E-mail(s) |
jsaba1@jhmi.edu
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| Phone |
7038968025
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| Organization name |
Johns Hopkins
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| Department |
Molecular Biology and Genetics
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| Lab |
Rachel Green
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| Street address |
725 N Wolfe St, 714 PCTB
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21231 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA764906 |
| SRA |
SRP338051 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE184515_RAW.tar |
23.1 Mb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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