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

作者：Tebaldi Toma; Zuccotti Paola; Peroni Daniele; Koehn Marcel; Gasperini Lisa; Potrich Valentina; Bonazza Veronica; Dudnakova Tatiana; Rossi Annalisa; Sanguinetti Guido; Conti Luciano; Macchi Paolo; D'Agostino Vito; Viero Gabriella; Tollervey David; Huettelmaier Stefan; Quattrone Alessandro^*

来源：Molecular Cell, 2018, 71(2): 256-+.

DOI：10.1016/j.molcel.2018.06.032

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.

• 出版日期2018-7-19