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Series GSE94690 Query DataSets for GSE94690
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
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.

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
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
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Submission date Feb 08, 2017
Last update date Oct 10, 2019
Contact name Ania Wilczynska
Organization name Beatson Insistute for Cancer Research
Street address Switchback Road
City Glasgow
ZIP/Postal code G61 1BD
Country United Kingdom
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (40)
GSM2480925 Total_RNA_RIPseq_rep1
GSM2480926 Total_RNA_RIPseq_rep2
GSM2480927 Total_RNA_RIPseq_rep3
BioProject PRJNA371822
SRA SRP099077

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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
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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