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| Status |
Public on Oct 09, 2019 |
| Title |
eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5’UTR |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Background: Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood.
Results: Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4- Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA-selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5’UTR of target mRNAs directly upstream of the AUG start codon.
Conclusions: Our data support a model whereby purine motifs towards the 3’ end of the 5’UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.
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| Overall design |
RIP-Seq of endogenous IPs of eIF4A1, eIF4A2 ad DDX6 with total RNA; RNA-Seq of subpolysomal and polysomal fractions from sucrose density gradients from HEK293 cells treated with control siRNA or CNOT1 siRNA with total RNA; RNA-Seq of total RNA of HEK293 cells transfected with either a control siRNA or siRNA against TNRC6A and TNRC6B
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| Contributor(s) |
Wilczynska A, Gillen SL, Meijer HA, Langlais C, Jukes-Jones R, Lu W, Godfrey JD, Hawley BR, Cain K, Le Quesne J, Bushell M, Schmidt T |
| Citation(s) |
31791371 |
| Submission date |
Feb 08, 2017 |
| Last update date |
Jan 16, 2020 |
| Contact name |
Ania Wilczynska |
| E-mail(s) |
awilcz@gmail.com
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| Organization name |
Beatson Insistute for Cancer Research
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| Street address |
Switchback Road
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| City |
Glasgow |
| ZIP/Postal code |
G61 1BD |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA371822 |
| SRA |
SRP099077 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94690_RAW.tar |
7.7 Mb |
(http)(custom) |
TAR (of TAB, TXT) |
| GSE94690_merged_IP_data_all_IPs.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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