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Status |
Public on Mar 01, 2023 |
Title |
Start codon-associated ribosomal frameshifting mediates nutrient stress adaptation |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
A translating ribosome is typically thought to follow the reading frame defined by the selected start codon. Using super-resolution ribosome profiling, here we report pervasive out-of-frame translation from the start codon. Unlike programmable frameshifting during elongation, start codon-associated ribosome frameshifting (SCARF) stems from the slippage of the initiating ribosome. Using a massively paralleled reporter assay, we uncovered sequence elements acting as SCARF enhancers or repressors, implying that start codon recognition is coupled with reading frame fidelity. This finding explains thousands of mass spectrometry spectra unannotated from human proteome. Mechanistically, we find that the eukaryotic initiation factor 5B (eIF5B) maintains the reading frame fidelity during the transition from initiation to elongation. Intriguingly, amino acid starvation induces SCARF by proteasomal degradation of eIF5B. The stress-induced SCARF products provide a degradative source to mitigate amino acid scarcity during starvation. Our findings illustrate the beneficial effect of divergent translation in nutrient stress adaptation.
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Overall design |
Ezra-seq in different cells or mouse tissues
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Contributor(s) |
Mao Y, Jia L, Qian S |
Citation missing |
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Submission date |
Sep 27, 2021 |
Last update date |
Mar 04, 2023 |
Contact name |
Yuanhui Mao |
E-mail(s) |
maoyuanhui123@gmail.com
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Organization name |
Zhejiang University
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Street address |
1369 West Wenyi Road
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City |
Hangzhou |
State/province |
Zhejiang |
ZIP/Postal code |
310000 |
Country |
China |
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Platforms (2) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (15)
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Relations |
BioProject |
PRJNA766610 |
SRA |
SRP338863 |