eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5’UTR

Autor: Claudia Langlais, Benjamin R. Hawley, Sara Zanivan, Sarah L. Gillen, Martin Bushell, Tobias Schmidt, Jack D. Godfrey, Kelvin Cain, John Le Quesne, Wei-Ting Lu, Hedda A. Meijer, Kari Kopra, Ania Wilczynska, Kelly Hodge, Rebekah Jukes-Jones
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Genome Biology, Vol 20, Iss 1, Pp 1-21 (2019)
Genome Biology
ISSN: 1474-760X
Popis: BackgroundRegulation 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.ResultsHere, 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.ConclusionsOur 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.
Databáze: OpenAIRE
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