February 17, 1989 - February 17, 2022

  • Date:12TuesdayFebruary 2019

    eIF1A promotes translation of cell cycle genes

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    10:00 - 10:30
    Nella and Leon Benoziyo Building for Biological Sciences
    Urmila Sehrawat
    Department of Biomolecular Sciences-WIS
    Department of Biomolecular Sciences
    AbstractShow full text abstract about Protein synthesis is linked to cell proliferation and its de...»
    Protein synthesis is linked to cell proliferation and its deregulation contributes to diseases such as cancer. eIF1A plays a key role in scanning and AUG selection and differentially affects translation of distinct mRNAs. Its unstructured N-terminal tail (NTT) is frequently mutated in several malignancies. Here, we show that eIF1A is essential for cell proliferation and cell-cycle progression. Ribosome-profiling of eIF1A knockdown cells revealed a substantial reduction in protein synthesis, with particular enrichment of cell-cycle mRNAs. The downregulated genes are predominantly characterized by lengthy 5’UTR. On the other hand, eIF1A depletion caused a broad stimulation of initiation in 5’UTRs at near-cognate AUG. Importantly, cancer-associated eIF1A-NTT mutants augment the positive effect of eIF1A on long 5’UTR while hardly affecting AUG selection. Our findings suggest that reduced binding of eIF1A NTT mutants to the ribosome retains its open state and facilitate scanning of long 5’UTR-containing cell cycle genes.