Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for post-transcriptional control

Christopher j. Kershaw, Michael g. Nelson, Lydia m. Castelli, Martin d. Jennings, Jennifer Lui, David Talavera, Chris m. Grant, Graham d. Pavitt, Simon j. Hubbard, Mark p. Ashe

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The regulation of translation provides a rapid and direct mechanism to modulate the cellular proteome. In eukaryotes, an established model for the recruitment of ribosomes to mRNA depends upon a set of conserved translation initiation factors. Nevertheless, how cells orchestrate and define the selection of individual mRNAs for translation, as opposed to other potential cytosolic fates, is poorly understood. We have previously found significant variation in the interaction between individual mRNAs and an array of translation initiation factors. Indeed, mRNAs can be separated into different classes based upon these interactions to provide a framework for understanding different modes of translation initiation. Here, we extend this approach to include new mRNA interaction profiles for additional proteins involved in shaping the cytoplasmic fate of mRNAs. This work defines a set of seven mRNA clusters, based on their interaction profiles with 12 factors involved in translation and/or RNA binding. The mRNA clusters share both physical and functional characteristics to provide a rationale for the interaction profiles. Moreover, a comparison with mRNA interaction profiles from a host of RNA binding proteins (RBPs) suggests that there are defined patterns in the interactions of functionally related mRNAs. Therefore, this work defines global cytoplasmic mRNA binding modules that likely coordinate the synthesis of functionally related proteins.
Original languageEnglish
Article number105195
JournalJournal of Biological Chemistry
Issue number105195
Publication statusPublished - 24 Aug 2023


  • mRNA
  • translation initiation
  • mRNA decay
  • RNA binding proteins
  • RIP-sequencing (RIP-seq)


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