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.

HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA / Tebaldi, Toma; Zuccotti, Paola; Peroni, Daniele; Köhn, Marcel; Gasperini, Lisa; Potrich, Valentina; Bonazza, Veronica; Dudnakova, Tatiana; Rossi, Annalisa; Sanguinetti, Guido; Conti, Luciano; Macchi, Paolo; D'Agostino, Vito; Viero, Gabriella; Tollervey, David; Hüttelmaier, Stefan; Quattrone, Alessandro. - In: MOLECULAR CELL. - ISSN 1097-2765. - STAMPA. - 71:2(2018), pp. 256-270.e10. [10.1016/j.molcel.2018.06.032]

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

Tebaldi, Toma;Zuccotti, Paola;Peroni, Daniele;Gasperini, Lisa;Potrich, Valentina;Bonazza, Veronica;Rossi, Annalisa;Conti, Luciano;Macchi, Paolo;D'Agostino, Vito;Quattrone, Alessandro
2018-01-01

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 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.
2
Tebaldi, Toma; Zuccotti, Paola; Peroni, Daniele; Köhn, Marcel; Gasperini, Lisa; Potrich, Valentina; Bonazza, Veronica; Dudnakova, Tatiana; Rossi, Annalisa; Sanguinetti, Guido; Conti, Luciano; Macchi, Paolo; D'Agostino, Vito; Viero, Gabriella; Tollervey, David; Hüttelmaier, Stefan; Quattrone, Alessandro
HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA / Tebaldi, Toma; Zuccotti, Paola; Peroni, Daniele; Köhn, Marcel; Gasperini, Lisa; Potrich, Valentina; Bonazza, Veronica; Dudnakova, Tatiana; Rossi, Annalisa; Sanguinetti, Guido; Conti, Luciano; Macchi, Paolo; D'Agostino, Vito; Viero, Gabriella; Tollervey, David; Hüttelmaier, Stefan; Quattrone, Alessandro. - In: MOLECULAR CELL. - ISSN 1097-2765. - STAMPA. - 71:2(2018), pp. 256-270.e10. [10.1016/j.molcel.2018.06.032]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/256499
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