HuD is a neural translation enhancer acting on mTORC1-responsive genes and counteracted by the Y3 small non-coding RNA

Toma Tebaldi, Paola Zuccotti, Daniele Peroni, Marcel Köhn, Lisa Gasperini, Valentina Potrich, Veronica Bonazza, Tatiana Dudnakova, Annalisa Rossi, Guido Sanguinetti, Luciano Conti, Paolo Macchi, Vito D'Agostino, Gabriella Viero, David Tollervey, Stefan Hüttelmaier, Alessandro Quattrone

Research output: Contribution to journalArticlepeer-review

Abstract

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 1304 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.
Original languageEnglish
Pages (from-to)256-270
Number of pages26
JournalMolecular Cell
Volume71
Issue number2
DOIs
Publication statusPublished - 19 Jul 2018

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