4.8 Article

HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA

Journal

MOLECULAR CELL
Volume 71, Issue 2, Pages 256-+

Publisher

CELL PRESS
DOI: 10.1016/j.molcel.2018.06.032

Keywords

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Funding

  1. Provincia Autonoma di Trento, Grande Progetto PAT AxonomiX
  2. Fondazione Cassa di Risparmio di Trento e Rovereto, Convenzione UniTrento Fondazione Caritro
  3. Wellcome Trust [109916]
  4. Deutsche Forschungsgemeinschaft [Hu1547/9-1]

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The RNA-binding protein HuD promotes neurogenesis and favors recovery from peripheral axon injury. HuD interacts with many mRNAs, altering both stability and translation efficiency. We generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells, identifying HuD target sites in 1,304 mRNAs, almost exclusively in the 3' UTR. HuD binds many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlates with the translation efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target is the abundant, small non-coding RNA Y3, amounting to 70% of the HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its recruitment to polysomes and its activity as a translation and neuron differentiation enhancer. These findings uncover an alternative route to the mTORC1 pathway for translational control in motor neurons that is tunable by a small non-coding RNA.

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