eIF3 targets cell-proliferation messenger RNAs for translational activation or repression.

Nature

1] Department of Molecular &Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Center for RNA Systems Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA [4] Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.

Published: June 2015

Regulation of protein synthesis is fundamental for all aspects of eukaryotic biology by controlling development, homeostasis and stress responses. The 13-subunit, 800-kilodalton eukaryotic initiation factor 3 (eIF3) organizes initiation factor and ribosome interactions required for productive translation. However, current understanding of eIF3 function does not explain genetic evidence correlating eIF3 deregulation with tissue-specific cancers and developmental defects. Here we report the genome-wide discovery of human transcripts that interact with eIF3 using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). eIF3 binds to a highly specific program of messenger RNAs involved in cell growth control processes, including cell cycling, differentiation and apoptosis, via the mRNA 5' untranslated region. Surprisingly, functional analysis of the interaction between eIF3 and two mRNAs encoding the cell proliferation regulators c-JUN and BTG1 reveals that eIF3 uses different modes of RNA stem-loop binding to exert either translational activation or repression. Our findings illuminate a new role for eIF3 in governing a specialized repertoire of gene expression and suggest that binding of eIF3 to specific mRNAs could be targeted to control carcinogenesis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603833PMC
http://dx.doi.org/10.1038/nature14267DOI Listing

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Article Synopsis
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  • This study examined how eIF3's binding to specific 5'-untranslated regions (5'-UTRs) of mRNAs leads to varying protein outputs, finding that it binds to a specific motif, AMAYAA, in some 5'-UTRs.
  • The study demonstrates that mRNAs bound by eIF3 have higher ribosome density and are preferentially translated during stress, highlighting eIF3's role as a novel translational enhancer.
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